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Safety and Pharmacokinetics Study of DM1157 to Treat Malaria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03490162
Recruitment Status : Terminated (There was toxicity in higher dose groups and a therapeutic dose level was not found in lower dose groups.)
First Posted : April 6, 2018
Last Update Posted : November 18, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE March 29, 2018
First Posted Date  ICMJE April 6, 2018
Last Update Posted Date November 18, 2019
Actual Study Start Date  ICMJE July 31, 2018
Actual Primary Completion Date September 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
  • Count of participants who discontinued single ascending dose (SAD) for safety reasons [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for a single dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD) [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of abnormal ECG changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD) [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for a single dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for multiple ascending dose (MAD) [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of abnormal vital sign changes from baseline (categorized as clinical Adverse Events (AEs)) for single ascending dose (SAD) [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of Adverse Events (AE) for a single dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of Adverse Events (AE) for multiple ascending dose (MAD) [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of Adverse Events (AE) for single ascending dose (SAD) [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory Adverse Events (AE) for a single dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory Adverse Events (AE) for multiple ascending dose (MAD) [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of laboratory Adverse Events (AE) for single ascending dose (SAD) [ Time Frame: Day 1 through Day 14 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
  • Changes in blood pressure in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in blood pressure in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in blood pressure in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in blood pressure in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in blood pressure in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in blood pressure in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in blood pressure in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in blood pressure in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in blood pressure in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in blood pressure in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in heart rate in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in heart rate in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in heart rate in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in heart rate in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in heart rate in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in temperature in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in temperature in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in temperature in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • Changes in temperature in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • Changes in temperature in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  • Number of patients who discontinue study drug due to safety reasons in Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • ECG changes: arrhythmia in a 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: arrhythmia in a 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: arrhythmia in a 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: arrhythmia in a 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: arrhythmia in a 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: arrhythmia in a 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: arrhythmia in a 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: arrhythmia in a 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: arrhythmia in a 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: arrhythmia in a 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: arrhythmia in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: PR Interval in 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: PR Interval in 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: PR Interval in 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: PR Interval in 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: PR Interval in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in a 150 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: QTc/QTch in a 150 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in a 300 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: QTc/QTch in a 300 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in a 45 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in a 600 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: QTc/QTch in a 600 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in a 9 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in a 900 mg Multiple Ascending Dose [ Time Frame: Day -1 through Day 18 ]
  • ECG changes: QTc/QTch in a 900 mg Single Ascending Dose [ Time Frame: Day -1 through Day 14 ]
  • ECG changes: QTc/QTch in Food Effect dose [ Time Frame: Day -1 through Day 14 ]
  • Occurrence of laboratory AEs in 150 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of laboratory AEs in 150 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory AEs in 300 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of laboratory AEs in 300 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory AEs in 45 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory AEs in 600 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of laboratory AEs in 600 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory AEs in 9 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory AEs in 900 mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of laboratory AEs in 900 mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of laboratory AEs in Food Effect dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 150-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited AEs in a 150-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 300-mg dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 300-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited AEs in a 300-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 45-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 600-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited AEs in a 600-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 9-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited AEs in a 900-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited AEs in a 900-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 150-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited SAEs in a 150-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 300-mg dose taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 300-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited SAEs in a 300-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 45-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 600-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited SAEs in a 600-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 9-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
  • Occurrence of unsolicited SAEs in a 900-mg Multiple Ascending Dose [ Time Frame: Day 1 through Day 18 ]
  • Occurrence of unsolicited SAEs in a 900-mg Single Ascending Dose [ Time Frame: Day 1 through Day 14 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 2, 2019)
  • Plasma levels of a single dose of DM1157 taken after food ingestion [ Time Frame: Day 1 through Day 14 ]
  • Plasma levels of multiple ascending dose (MAD) of DM1157 [ Time Frame: Day 1 through Day 18 ]
  • Plasma levels of single ascending dose (SAD) of DM1157 [ Time Frame: Day 1 through Day 14 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2018)
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Apparent total clearance of the drug from plasma after oral administration (CL/F) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve extrapolated to infinity (AUC0-inf) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Area under the concentration time-curve to the last concentration above the lower limit of quantitation (AUC0-last) for Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Elimination rate constant (Ke) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Elimination rate constant (Ke) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Elimination rate constant (Ke) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Elimination rate constant (Ke) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Elimination rate constant (Ke) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Maximum observed concentration (Cmax) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Maximum observed concentration (Cmax) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Maximum observed concentration (Cmax) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Maximum observed concentration (Cmax) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Maximum observed concentration (Cmax) for Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Oral volume of distribution (V/F) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Oral volume of distribution (V/F) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Oral volume of distribution (V/F) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Oral volume of distribution (V/F) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Oral volume of distribution (V/F) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Terminal elimination half-life (t½) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Terminal elimination half-life (t½) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Terminal elimination half-life (t½) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Terminal elimination half-life (t½) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Terminal elimination half-life (t½) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) for 150 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Time of maximum observed concentration (Tmax) for 150 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) for 300 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Time of maximum observed concentration (Tmax) for 300 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) for 45 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) for 600 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Time of maximum observed concentration (Tmax) for 600 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) for 9 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) for 900 mg in Multiple Ascending Dose [ Time Frame: Day 1 through Day 8 ]
  • Time of maximum observed concentration (Tmax) for 900 mg in Single Ascending Dose [ Time Frame: Day 1 through Day 6 ]
  • Time of maximum observed concentration (Tmax) in Food Effect Dose [ Time Frame: Day 1 through Day 6 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Pharmacokinetics Study of DM1157 to Treat Malaria
Official Title  ICMJE A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses and Effect of Food on the Pharmacokinetics of DM1157 in Healthy Adults
Brief Summary This is a phase 1 trial to evaluate the safety and pharmacokinetics of single and multiple ascending doses and effect of food on the pharmacokinetics of a novel antimalarial drug in healthy adults. The study will enroll 104 healthy volunteers, males and females, aged 18 to 45 years and will consists of 3 parts: Part 1, Single Ascending Dose (SAD); Part 2, Multiple Ascending Dose (MAD); and Part 3, Food Effect. Part 2 and Part 3 may be initiated after a Safety Monitoring Committee (SMC) review and approval of the of Part 1 safety data. Study duration will be 16 months with patient participation duration 14 days for SAD and Food Effect, and 18 days for MAD. The primary objectives of this study are to: 1) assess the safety and tolerability of single doses of DM1157 at levels ranging from 9 mg to 900 mg; 2) assess the safety and tolerability of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the safety and tolerability of DM1157 administered with or without food.
Detailed Description This is a first-in-humans, phase 1, randomized, double-blind, single-site, placebo-controlled study in 104 healthy volunteers, males and females, aged 18 to 45 years inclusive. The study will consists of 3 parts: Part 1, Single Ascending Dose (SAD) - participants will be administered a single dose (ranges from 9 mg to 900 mg) of DM1157 orally after fasting or a matching placebo; Part 2, Multiple Ascending Dose (MAD) - participants will be administered three doses (ranges from 150 mg to 900 mg) of DM1157 orally once daily for three days after fasting or a matching placebo; and Part 3, Food Effect - participants will be administered 300 mg of DM1157 orally with high fat meal or a matching placebo. Part 2 and Part 3 may be initiated after a Safety Monitoring Committee (SMC) review and approval of the of Part 1 safety data. Study duration will be 16 months with patient participation duration 14 days for SAD and Food Effect, and 18 days for MAD. The primary objectives of this study are to: 1) assess the safety and tolerability of single doses of DM1157 at levels ranging from 9 mg to 900 mg; 2) assess the safety and tolerability of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the safety and tolerability of DM1157 administered with or without food. The secondary objectives are to: 1) assess the PK of single doses of DM1157 at levels ranging from 9 mg to 900 mg, including dose proportionality; 2) assess the PK of DM1157 administered as single daily doses for 3 days at levels ranging from 150 mg to 900 mg; 3) assess the PK of 300 mg DM1157 administered with or without food, including determination of the presence or absence of a food effect on exposure.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Malaria
Intervention  ICMJE
  • Drug: DM1157
    DM1157 is a novel anti-malarial drug that is derived from chloroquine. DM1157 maintains the efficacy of chloroquine and has molecular features that overcome resistance to chloroquine.
  • Other: Placebo
    Placebo
Study Arms  ICMJE
  • Experimental: Food Effect
    300 mg of DM1157 (2 capsules of 150 mg) orally with high fat diet, n=6, and matching placebo (2 capsules) orally with high fat diet, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: MAD 1
    150 mg of DM1157 (1 capsule) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (1 capsule) orally daily for three days with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: MAD 2
    300 mg of DM1157 (2 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (2 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: MAD 3
    600 mg of DM1157 (4 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (4 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: MAD 4
    900 mg of DM1157 (6 capsules of 150 mg) orally daily for three days with 240 ml of water after an overnight fast, n=8, and matching placebo (6 capsules) orally daily for three days with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 1
    9 mg of DM1157 (1 capsule) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (1 capsule) orally with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 2
    27 mg of DM1157 (3 capsules of 9 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (3 capsules) orally with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 3
    81 mg of DM1157 (9 capsules of 9 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (9 capsule) orally with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 4
    150 mg of DM1157 (1capsule) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (1 capsule) orally with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 5
    300 mg of DM1157 (2 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (2 capsules) orally with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 6
    600 mg of DM1157 (4 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (4 capsules) orally with 240 ml of water after an overnight fast, n=2
    Interventions:
    • Drug: DM1157
    • Other: Placebo
  • Experimental: SAD 7
    900 mg of DM1157 (6 capsules of 150 mg) orally with 240 ml of water after an overnight fast, n=6, and matching placebo (6 capsules) orally with 240 ml of water after an overnight fast (n=2)
    Interventions:
    • Drug: DM1157
    • Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 14, 2019)
50
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2018)
96
Actual Study Completion Date  ICMJE September 6, 2019
Actual Primary Completion Date September 6, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Is a healthy male or nonpregnant female age 18 to 45 years, inclusive.
  2. Can understand the informed consent process and procedures.
  3. Agrees to be available for all study visits.
  4. If a woman of childbearing potential, agrees to use 2 acceptable contraception methods from 30 days before first study drug administration until 90 days after last study drug administration.

    -Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, nonsurgical, nonhormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or less than 1 year of the last menses if menopausal.

    -- Includes, but is not limited to, nonmale sexual relationships, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more before the subject receives the first study drug dose, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables, or oral contraceptives. If sexually active, methods can include condoms, spermicidal gel, diaphragm, hormonal or nonhormonal intrauterine device, surgical sterilization, oral contraceptive pill, and depot progesterone injections.

  5. If male, agrees to use a barrier method of birth control from 30 days before first study drug administration until 90 days after last study drug administration.
  6. Has adequate venous access for blood draws.
  7. Body mass index (BMI) 18 to 35 kg/m^2, inclusive.

Exclusion Criteria:

  1. Any medical disease or condition that, in the opinion of the site PI or appropriate sub investigator, is a contraindication to study participation.
  2. History of clinically significant ECG abnormalities or has clinically significant ECG abnormalities at Screening.
  3. Use of any prescription medication (excluding oral contraceptive pills in females) within 14 days before first study drug administration.
  4. Use of occasional nonprescription drugs (oral or topical) within 7 days before first study drug administration unless permitted by the investigator.

    - Nonprescription drugs include vitamins, antacids, herbal or dietary supplements, and topical gels, creams, etc., that in the opinion of the site PI could interfere with the study drug.

  5. Hypertension with confirmed systolic blood pressure (BP) greater than 145 mm Hg or confirmed diastolic BP greater than 90 mm Hg, measured after 10 to 15 minutes of rest.
  6. Heart rate (HR) less than 50 bpm or greater than 100 bpm.
  7. Body weight less than 50 kg.
  8. History of a significant illness within 2 weeks before dosing (subjects can screen after illness is resolved for 2 weeks).
  9. History of hemolytic anemia.
  10. History of retinal eye disease.
  11. History of hearing loss.
  12. History of seizures.
  13. History of thyroid disease or currently on replacement therapy for hypothyroidism.
  14. History of liver disease other than Gilbert's syndrome.
  15. History of severe drug hypersensitivity, including a severe allergic reaction, anaphylaxis, or convulsions following any medication, vaccination, or infusion.
  16. History of malignancy except low-grade skin cancer (ex. basal cell carcinoma thought to be cured).
  17. Known diagnosis of prolonged QT interval, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
  18. History of drug or alcohol abuse within 12 months before Screening.
  19. History of renal disease.
  20. Excessive consumption of beverages containing xanthine bases, including Red Bull, chocolate, etc., or more than 400 mg of caffeine per day (more than 4 cups of coffee per day).
  21. Consumption of citrus fruits or juices (ex. pomegranate, orange, lime, grapefruit) within 7 days before first study drug administration.
  22. Use of nicotine-containing products within 30 days before Screening and until completion of study.
  23. Consumption of alcohol within 24 hours of first study drug administration.
  24. Has any condition or disease that might affect drug absorption, distribution, or excretion (ex. gastrectomy, diarrhea).
  25. Positive serology results for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
  26. Positive drug screen (cannabinoids, amphetamines, barbiturates, cocaine, opiates, benzodiazepines, phencyclidine) or positive breathalyzer test for alcohol.

    - Subjects should be notified by phone not to consume any poppy seeds within 24 hours before the Screening blood test to avoid false a positive opioid test result.

  27. History of allergic reaction or intolerance to CQ.
  28. Males with a QTcF greater than 450 ms or females with a QTcF greater than 460 ms (Fridericia's correction) at Screening.
  29. Positive pregnancy test within 24 hours before study drug administration; pregnant or nursing.
  30. Screening lab tests, specifically total WBC, platelet count, hemoglobin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine, which meet Grade 1 or higher toxicity. Safety laboratory tests drawn on Day -1 will serve as baseline. Day -1 safety laboratory tests with a Grade 1 severity will not exclude a subject from participation if assessed as not clinically significant by the PI or designee.
  31. Any specific condition that, in the judgment of the site PI, precludes participation because it could affect subject safety.
  32. Received an experimental agent within 30 days or 5 half-lives (whichever is longer) before study drug administration.

    - Vaccine, drug, biologic, device, blood product, or medication

  33. Is participating or plans to participate in another clinical study with an interventional agent that will be received during participation in this study.
  34. Has donated more than 500 mL of blood within the last month before Screening.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03490162
Other Study ID Numbers  ICMJE 16-0088
HHSN272201500006I
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP