A Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects

A Single-center, Double-blind, Randomized, Placebo-controlled Phase 1 Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects

A safety and tolerability study in healthy subjects including examination of how the body takes up, distributes, and gets rid of ACT-1014-6470

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: ACT-1014-6470; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Parexel International GmbH Klinikum Westend

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

General criteria

• Signed informed consent prior to any study-mandated procedure.
• Healthy male subjects (both study parts) and female subjects of nonchildbearing potential (Part B) aged between 18 and 55 years (inclusive) at Screening.
• Healthy on the basis of medical history, physical examination, cardiovascular assessments, and clinical laboratory tests.
• Male subjects with a partner that might become pregnant must either be vasectomized or agree to practice adequate contraception from admission to the study site until 3 months after dosing, or the partner must consistently and correctly use (from Screening, during the entire study, and for at least 3 months after last study treatment intake) a highly effective method of contraception.

Criteria for Part B only:

• Women of non-childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day-1.

Exclusion Criteria:

• Previous exposure to the study medication.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment.
• Relevant bacterial, viral, fungal, or protozoal infection that manifested within the last 6 weeks prior to Screening and/or ongoing relevant bacterial, viral, fungal, or protozoal infection, as judged by the investigator, and/or evidence of immune dysfunction based on laboratory tests at Screening.
• Any signs or symptoms of active, ongoing infection judged to be clinically relevant by the investigator (special attention should be given to clinical signs and symptoms consistent with COVID-19, e.g., fever, dry cough, dyspnea, sore throat, or fatigue).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT-1014-6470 single dose (dose level 1); Soft capsule for oral administration	Drug: ACT-1014-6470; Soft capsules for oral administration
Placebo Comparator: Placebo single dose (dose level 1); Soft capsule for oral administration	Drug: Placebo; Soft capsules for oral administration
Experimental: ACT-1014-6470 single dose (dose level 2); Soft capsule for oral administration	Drug: ACT-1014-6470; Soft capsules for oral administration
Placebo Comparator: Placebo single dose (dose level 2); Soft capsule for oral administration	Drug: Placebo; Soft capsules for oral administration
Experimental: ACT-1014-6470 multiple dose (dose level 1); Soft capsule for oral administration	Drug: ACT-1014-6470; Soft capsules for oral administration
Placebo Comparator: Placebo multiple dose (dose level 1); Soft capsule for oral administration	Drug: Placebo; Soft capsules for oral administration
Experimental: ACT-1014-6470 multiple dose (dose level 2); Soft capsule for oral administration	Drug: ACT-1014-6470; Soft capsules for oral administration
Placebo Comparator: Placebo multiple dose (dose level 2); Soft capsule for oral administration	Drug: Placebo; Soft capsules for oral administration
Experimental: ACT-1014-6470 multiple dose (dose level 3); Soft capsule for oral administration	Drug: ACT-1014-6470; Soft capsules for oral administration
Placebo Comparator: Placebo multiple dose (dose level 3); Soft capsule for oral administration	Drug: Placebo; Soft capsules for oral administration
Experimental: ACT-1014-6470 multiple dose (dose level 4); Soft capsule for oral administration	Drug: ACT-1014-6470; Soft capsules for oral administration
Placebo Comparator: Placebo multiple dose (dose level 4); Soft capsule for oral administration	Drug: Placebo; Soft capsules for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety profile including incidence of treatment-emergent adverse events.	Safety and tolerability assessments will be performed at predefined time points from Day 1 to Day 4 in Part A and Day 1 to Day 10 in Part B (total duration: max. 50 days).

Secondary Outcome Measures

Outcome Measure	Time Frame
Part A - Single ascending dose (SAD): Area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t).	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).
Part A - Single ascending dose (SAD): Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf).	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).
Part A - Single ascending dose (SAD): Maximum plasma concentration (Cmax).	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).
Part A - Single ascending dose (SAD): Time to reach Cmax (tmax).	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).
Part A - Single ascending dose (SAD): Terminal half-life (t½).	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 4 (total duration: max. 4 days).
Part B - Multiple ascending dose (MAD): AUC during a dosing interval (AUCτ) following the first and the last dose.	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).
Part B - Multiple ascending dose (MAD): Cmax of the first and the last dosing interval.	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).
Part B - Multiple ascending dose (MAD): tmax of the first and the last dosing interval.	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).
Part B - Multiple ascending dose (MAD): t½ after last dose administration.	Blood samples for the determination of the PK parameters will be collected at predefined time points from Day 1 to Day 10 (total duration: max. 10 days).

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): September 20, 2021
• Study Completion (Actual): September 20, 2021

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): October 15, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: ID-087-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No