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Single Oral Dose Escalation Study of DNDI-0690 in Healthy Male Subjects

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ClinicalTrials.gov Identifier: NCT03929016
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Information provided by (Responsible Party):
Drugs for Neglected Diseases

Brief Summary:
This study will evaluate how the test medicine DNDI-0690 is taken up and broken down by the body and will also look at the safety and tolerability of the test medicine after a single dose. This is the first time the test medicine DNDI-0690 will be administered to humans.

Condition or disease Intervention/treatment Phase
Visceral Leishmaniasis Cutaneous Leishmaniases Drug: DNDI-0690 Drug: Placebo of DNDI-0690 Phase 1

Detailed Description:
DNDI-0690 is intended to be used as oral treatment for Visceral Leishmaniasis with potential for the cutaneous form of the disease, Cutaneous Leishmaniasis. The present protocol describes the first-in-human (FIH) study with DNDI-0690.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Single Ascending Dose
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double Blind
Primary Purpose: Treatment
Official Title: A Phase I, Double-blind, Randomised, Single Centre, Parallel Group, Single-dose, Dose-escalation, Placebo Controlled Study of the Safety, Tolerability and Pharmacokinetics of DNDI-0690 After Oral Dosing in Healthy Male Subjects
Actual Study Start Date : April 2, 2019
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active DNDI-0690
Single dose starting from 10 mg for the first cohort. Dose for following cohorts to be decided by the Safety Review Committee
Drug: DNDI-0690
capsules of 10, 100 and 200 mg

Placebo Comparator: Placebo
Single dose placebo
Drug: Placebo of DNDI-0690
capsules of matching placebo




Primary Outcome Measures :
  1. Safety and Tolerability of DNDI-0690 by Assessing the Occurrence of Treatment-emergent adverse events (TEAEs) [ Time Frame: from baseline up to 7-10 days post-dose ]
    number of subjects experiencing TEAEs classified by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class and Preferred Terms

  2. Safety and Tolerability of DNDI-0690 by Assessing the Changes in vital signs (pulse rate) [ Time Frame: from baseline up to 7-10 days post-dose ]
    Pulse rate (beats per minute)

  3. Safety and Tolerability of DNDI-0690 by Assessing the Changes in vital signs (blood pressure) [ Time Frame: from baseline up to 7-10 days post-dose ]
    Blood pressure (mmHg)

  4. Safety and Tolerability of DNDI-0690 by Assessing the Changes in 12-lead electrocardiogram (ECG) parameters [ Time Frame: from baseline up to 7-10 days post-dose ]
    corrected QT interval by Frideriecia's formula (QTcF) (msec)

  5. Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to liver function [ Time Frame: from baseline up 7-10 days post-dose ]
    aspartate aminotransferase (AST)

  6. Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to liver function [ Time Frame: from baseline up 7-10 days post-dose ]
    alanine aminotransferase (ALT)

  7. Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to renal function [ Time Frame: from baseline up 7-10 days post-dose ]
    creatinine (mg/dL)

  8. Safety and Tolerability of DNDI-0690 by Assessing the Changes of Safety laboratory parameters related to renal function [ Time Frame: from baseline up 7-10 days post-dose ]
    creatinine clearance (CLcr)

  9. Safety and Tolerability of DNDI-0690 by Assessing the Changes of Troponin I as a cardiac safety marker [ Time Frame: 4h, 9h, 24h and 48h post-dose ]
    Troponin I


Secondary Outcome Measures :
  1. Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity (AUC0-inf) [ Time Frame: pre-dose up to 72 hours post-dose ]
    To assess plasma pharmacokinetic parameters

  2. Observed Maximum Concentration (Cmax) [ Time Frame: pre-dose up to 72 hours post-dose ]
    To assess plasma pharmacokinetic parameters

  3. Time to Maximum Observed Plasma Concentration (Tmax) [ Time Frame: pre-dose up to 72 hours post-dose ]
    To assess plasma pharmacokinetic parameters

  4. Apparent elimination half-life (T1/2) [ Time Frame: pre-dose up to 72 hours post-dose ]
    To assess plasma pharmacokinetic parameters



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males
  • 18 to 55 years of age at the time of signing informed consent
  • Body mass index (BMI) of 18.0 to 30.1 kg/m2 as measured at screening
  • General good physical health determined by medical and surgical history, physical examination, 12-lead ECG, vital signs and clinical laboratory tests
  • Normal blood pressure: Systolic blood pressure between ≥90 and ≤140 mmHg, Diastolic blood pressure ≤90 mmHg, measured after 10 min rest in supine position at screening and pre-dose
  • A resting Heart Rate (HR) between ≥40 and ≤90 bpm measured after 10 min rest in supine position at screening and pre-dose
  • ECG recording without clinically significant abnormality, including QTcF measure of ≤450 msec at screening and pre-dose
  • Having had no febrile seizures or infectious illness for at least 7 days prior to administration of the Investigational Medicinal Product (IMP)
  • Must be willing and able to communicate and participate in the whole study
  • Must provide written informed consent
  • Must agree to adhere to the contraception requirements and life-style restrictions defined in the protocol

Exclusion Criteria:

  • Subjects who have received any IMP in a clinical research study within the 3 months or 90 days prior to Day 1
  • Subjects who are study site employees, or immediate family members of a study site or sponsor employee
  • Subjects who have previously been enrolled in this study and/or have received DNDI-0690 previously
  • History of any drug or alcohol abuse in the past 2 years
  • Demonstrating excess in caffeine/xanthine consumption (more than 6 cups of coffee or equivalent a day)
  • Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type). As confirmed by a positive alcohol breath test at screening or admission
  • Current smokers and those who have smoked within the last 12 months. As confirmed by a breath carbon monoxide reading of greater than 10 ppm at screening or admission
  • Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
  • Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
  • Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis (especially aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), creatinine, and blood urea nitrogen (BUN)) as judged by the investigator (laboratory parameters are listed in Appendix 1). Subjects with Gilbert's syndrome are allowed
  • Confirmed positive drugs of abuse test result
  • Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
  • Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <80 mL/min using the Cockcroft-Gault equation
  • History of clinically significant cardiovascular, renal, hepatic, neurological (especially seizures), immunological, psychiatric, myopathies, bleeding tendency, respiratory and particularly gastrointestinal (GI) disease, especially peptic ulceration and chronic gastritis, GI bleeding, ulcerative colitis, Crohn's Disease or Irritable Bowel Syndrome, as judged by the investigator
  • History of additional risk factors for Torsades des Pointe (eg heart failure, hypokalaemia, family history of long QT syndrome)
  • Rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency
  • Any relevant GI complaints within 7 days of dosing
  • Serious adverse reaction or clinically relevant hypersensitivity to any drug or the formulation excipients (Hypromellose [HPMC], sodium lauryl sulphate [SLS], sucrose, croscarmellose sodium and magnesium stearate)
  • Presence or history of clinically significant allergy requiring treatment (including asthma, urticaria, clinically significant allergic rash or other severe allergic diathesis), as judged by the investigator. Hay fever is allowed unless it is active
  • Donation or loss of greater than 500 mL of blood within the previous 3 months or more than 100 mL within 30 days before signing Informed Consent Form (ICF) to this trial
  • Subjects who are taking, or have taken, any prescribed or over-the-counter drug (including anti-acid drugs) or vitamins/herbal remedies (eg St. John's Wort and others which are known to interfere with the Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) metabolic pathways) in the 21 days before IMP administration. Administration of up to 4 g of paracetamol per day within 7 days of IMP administration is allowed
  • Surgery within 12 weeks prior to screening, with the exception of appendectomy
  • Any surgery (eg gastric bypass) or medical condition that may affect absorption of orally administered drugs
  • Failure to satisfy the investigator of fitness to participate for any other reason

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929016


Contacts
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Contact: Senior Clinical Manager +41 22 906 92 57 sblesson@dndi.org

Locations
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United Kingdom
Quotient Sciences Recruiting
Nottingham, United Kingdom
Contact: Project Manager    +44 (0)115 974 9000      
Sponsors and Collaborators
Drugs for Neglected Diseases
Investigators
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Principal Investigator: Sharan Sidhu, MD Quotient Sciences

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Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT03929016     History of Changes
Other Study ID Numbers: DNDi-0690-01
2018-002021-35 ( EudraCT Number )
QSC200932 ( Other Identifier: Quotient Sciences )
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in the publication will be shared at the time of publication of study results.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: at the time of publication of study results.
Access Criteria: not yet defined

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Drugs for Neglected Diseases:
First-in-human
single ascending dose
healthy volunteer

Additional relevant MeSH terms:
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Leishmaniasis
Leishmaniasis, Cutaneous
Leishmaniasis, Visceral
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases