A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-1014-6470 in Healthy Subjects

Healthy Clinical Trial

Official title:

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, Including Food Effect, Mass Balance, and Metabolite Profiling

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04183686
• Other study ID #: ID-087-101
• Status: Completed
• Phase: Phase 1
• Start date: November 25, 2019
• Est. completion date: March 15, 2020

Study information

• Verified date: August 2020
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-1014-6470 in healthy subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: March 15, 2020
• Est. primary completion date: March 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

General Inclusion Criteria:

• Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.

• Healthy male (Part A and B) and female subjects (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 who 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 a highly effective method of contraception.

Inclusion Criteria for Part B:

• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. They must consistently and correctly use a highly effective method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner.

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

General Exclusion Criteria:

• 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.

Exclusion Criteria for the ADME evaluation (Part A) only:

• Radiation exposure, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. Occupationally exposed workers, as defined in the relevant Ionising Radiation Regulations, must not participate in the study.

• Participation in any study involving administration of any 14C radiolabeled compound within the 12 months prior to Screening.

Exclusion Criteria for Part B:

• Pregnant or lactating women.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ACT-1014-6470 (SAD)
Single dose of ACT-1014-6470; soft capsules for oral use.
• ACT-1014-6470 (MAD)
Multiple doses of ACT-1014-6470; soft capsules for oral use.
• Placebo (SAD)
Single dose of matching placebo; soft capsules for oral use.
• Placebo (MAD)
Multiple doses of matching placebo; soft capsules for oral use.
• 14C-ACT-1014-6470 microtracer
Single dose of 14C-ACT-1014-6470 microtracer; soft capsules for oral use.
• 14C-ACT-1014-6470 microtracer placebo
Single dose of matching placebo; soft capsules for oral use.

Locations

Country	Name	City	State
Netherlands	PRA Health Sciences	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All cohorts: Maximum plasma concentration (Cmax).	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
Other	All cohorts: Time to reach Cmax (tmax).	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
Other	All cohorts: t½.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
Other	Food effect evaluation only: AUC0-inf under fasted conditions.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Other	Food effect evaluation only: Cmax under fasted conditions.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Other	Food effect evaluation only: tmax under fasted conditions.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Other	Food effect evaluation only: t½ under fasted conditions	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD)	Total duration of assessments: up to 3 weeks.
Other	Part B (MAD): AUC during a dosing interval (AUCt) following the first and the last dose.	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration)	Total duration of assessments: up to 3 weeks.
Other	Treatment-emergent adverse events (AEs)	From start of study treatment administration up to End-of-Study (EOS) or End-of-Period (EOP). - Treatment-emergent serious AEs from the start of the study treatment administration up to EOS or EOP.	Total duration of assessments: up to 3 weeks.
Other	Treatment-emergent serious adverse events (SAEs)	From start of study treatment administration up to End-of-Study (EOS) or End-of-Period (EOP). - Treatment-emergent serious AEs from the start of the study treatment administration up to EOS or EOP.	Total duration of assessments: up to 3 weeks.
Primary	All cohorts: Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf)	Blood samples for determination of PK parameters will be collected at predefined time points from Day 1 to Day 4 of Part A (SAD, Day 1 to Day 8 for ADME cohort A4) and from Day 1 to Day X+3 of Part B (MAD, with Day X = day of last study treatment administration).	Total duration of assessments: up to 3 weeks.