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Trial record 75 of 88505 for:    subjects

Study to Evaluate Safety and Tolerability of ACT-709478 in Healthy Subjects

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: NCT03165097
Recruitment Status : Completed
First Posted : May 24, 2017
Last Update Posted : December 24, 2019
Sponsor:
Information provided by (Responsible Party):
Idorsia Pharmaceuticals Ltd.

Tracking Information
First Submitted Date  ICMJE May 23, 2017
First Posted Date  ICMJE May 24, 2017
Last Update Posted Date December 24, 2019
Actual Study Start Date  ICMJE July 7, 2017
Actual Primary Completion Date November 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
  • Incidence of treatment-emergent adverse events [ Time Frame: up to Day 23 ]
    The percentage of subjects with treatment-emergent adverse events will be reported
  • Changes from baseline in vital signs [ Time Frame: up to Day 23 ]
    Vital signs include diastolic and systolic blood pressure and pulse rate
  • Incidence of any clinical relevant findings in ECG variables [ Time Frame: up to Day 23 ]
    The number of subjects with any treatment-emergent electrocardiogram (ECG) abnormalities will be reported
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
  • Maximum plasma concentration (Cmax) of ACT-709478 [ Time Frame: up to Day 23 ]
    Cmax is derived from the observed plasma concentration-time curves
  • Time to reach Cmax (tmax) of ACT-709478 [ Time Frame: up to Day 23 ]
    tmax is directly derived from the observed plasma concentrations
  • Terminal half-life (t1/2) of ACT-709478 [ Time Frame: up to Day 23 ]
    t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves
  • Area under the plasma concentration-time curve AUC(tau) of ACT-709478 [ Time Frame: up to Day 23 ]
    AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
  • Area under the plasma concentration-time curve AUC(tau) of midazolam [ Time Frame: 24 hours after dosing on Day 1, Day 22 and Day 30 ]
    AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
  • Time to reach Cmax (tmax) [ Time Frame: 24 hours after dosing on Day 1, Day 22 and Day 30 ]
    tmax is directly derived from the observed plasma concentrations
  • Maximum plasma concentration (Cmax) of ACT-709478 [ Time Frame: 24 hours after dosing on Day 1, Day 22 and Day 30 ]
    Cmax is derived from the observed plasma concentration-time curves
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2017)
  • Maximum plasma concentration (Cmax) of ACT-709478 [ Time Frame: up to Day 23 ]
    Cmax is derived from the observed plasma concentration-time curves
  • Time to reach Cmax (tmax) of ACT-709478 [ Time Frame: up to Day 23 ]
    tmax is directly derived from the observed plasma concentrations
  • Terminal half-life (t1/2) of ACT-709478 [ Time Frame: up to Day 23 ]
    t1/2 is calculated from the terminal rate constant obtained from the plasma concentrations-time curves
  • Area under the plasma concentration-time curve AUC(tau) of ACT-709478 [ Time Frame: up to Day 23 ]
    AUCtau is defined as the area under the plasma concentration-time curve during one dosing interval
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate Safety and Tolerability of ACT-709478 in Healthy Subjects
Official Title  ICMJE A Single-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Multiple-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-709478 in Healthy Subjects
Brief Summary The primary purpose of this study is to evaluate the safety and tolerability of ascending multiple doses of ACT-709478 in healthy male and female subjects
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Healthy Subjects
Intervention  ICMJE
  • Drug: ACT-709478
    Hard gelatine capsules for oral administration
  • Drug: Placebo
    Placebo capsules matching ACT-709478 capsules
  • Drug: Midazolam
    Midazolam oral solution (2 mg/mL) applied with a syringe
  • Drug: ACT-709478 combined with midazolam
    Hard gelatine capsules for oral administration (ACT-709478) to be taken first followed by Midazolam oral solution (2 mg/mL) applied with a syringe
Study Arms  ICMJE
  • Experimental: ACT-709478

    40 subjects will receive multiple doses of ACT-709478 at the planned dose levels of 30, 60, 100, and 200 mg.

    Each dose level will be investigated in a new cohort of 10 healthy male and female subjects (4 male subjects on active drug and 1 on placebo, 4 female subjects on active drug and 1 on placebo) undergoing one treatment period with a once daily dosing scheme.

    Intervention: Drug: ACT-709478
  • Placebo Comparator: Placebo
    Matched placebo administered accordingly
    Intervention: Drug: Placebo
  • Midazolam
    4 mg taken by mouth on Day 1 of the corresponding cohort
    Intervention: Drug: Midazolam
  • Experimental: ACT-709478 combined with Midazolam
    On Day 22 and Day 30, midazolam (4 mg) and ACT-709478 (60 mg or 100 mg) to be co-administered.
    Intervention: Drug: ACT-709478 combined with midazolam
Publications * Richard M, Kaufmann P, Ort M, Kornberger R, Dingemanse J. Multiple-Ascending Dose Study in Healthy Subjects to Assess the Pharmacokinetics, Tolerability, and CYP3A4 Interaction Potential of the T-Type Calcium Channel Blocker ACT-709478, A Potential New Antiepileptic Drug. CNS Drugs. 2020 Mar;34(3):311-323. doi: 10.1007/s40263-019-00697-1.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2019)
46
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2017)
40
Actual Study Completion Date  ICMJE December 28, 2018
Actual Primary Completion Date November 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent form
  • Healthy male and female subjects aged between 18 and 55 years (inclusive) at screening
  • Negative serum pregnancy tests at screening and negative urine pregnancy test at Day -1 for women and agreement to use 2 reliable methods of contraception for at least 3 months after last study drug administration
  • Body mass index of 18.0 to 29.9 kg/m2 (inclusive) at screening
  • Systolic blood pressure 100-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 50-90 bpm (inclusive), measured after 5 minutes in the supine position at screening and on Day -1
  • Healthy on the basis of physical examination, cardiovascular, ophthalmological, neurological assessments and laboratory tests

Exclusion Criteria:

  • Known hypersensitivity to ACT-709478 or drugs of the same class, or any of their excipients
  • History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatments
  • QT interval corrected with Fridericia's formula (QTcF) > 450 ms (using the ECG machine HR correction method) at screening and on Day -1
  • Treatment with another investigational treatment within 2 months or 5 t1/2 (whichever is the longest) prior to screening or participation in more than four investigational treatment studies within 1 year prior to screening
  • Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03165097
Other Study ID Numbers  ICMJE AC-083-102
2017-000336-34 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Idorsia Pharmaceuticals Ltd.
Study Sponsor  ICMJE Idorsia Pharmaceuticals Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Idorsia Pharmaceuticals Ltd.
PRS Account Idorsia Pharmaceuticals Ltd.
Verification Date December 2019

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