A Study to Examine the Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-ascending Doses of ACT-777991 in Healthy Subjects

NCT04798209 | Completed Phase 1

• 2 other identifiers: ID-089-1012020-004464-26
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

A study to examine the safety, tolerability, and pharmacokinetics of single- and multiple-ascending doses of ACT-777991 in healthy subjects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events.

  From first dose on Day 1 to Day 4 after the last dose was administered

Secondary Outcomes (12)

• All cohorts: 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) of ACT-777991

  Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered

• All cohorts: Area under the plasma concentration-time curve (AUC) from zero to infinity (AUC0-inf) of ACT-777991

  Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered

• All cohorts: Maximum plasma concentration (Cmax) of ACT-777991

  Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered

• All cohorts: Time to reach Cmax (tmax) of ACT-777991

  Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered

• All cohorts: Terminal half-life (t1/2) of ACT-777991

  Blood samples will be collected at predefined time points from Day 1 to Day 4 after the last dose was administered

Study Arms (15)

Part A (single ascending dose) Dose A1

EXPERIMENTAL

Single dose A1 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A2

EXPERIMENTAL

Single dose A2 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A3

EXPERIMENTAL

Single dose A3 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A4

EXPERIMENTAL

Single dose A4 of ACT-777991 under fasted and fed conditions, separated by at least 14 days.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A5

EXPERIMENTAL

Single dose A5 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A6

EXPERIMENTAL

Single dose A6 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A7

EXPERIMENTAL

Single dose A7 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part A (single ascending dose arm) Dose A8

EXPERIMENTAL

Single dose A8 of ACT-777991.

Drug: ACT-777991 (SAD); Drug: Placebo (SAD)

Part B (multiple ascending dose) Dose B1

EXPERIMENTAL

Multiple doses B1 of ACT-777991.

Drug: ACT-777991 (MAD); Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B2

EXPERIMENTAL

Multiple doses B2 of ACT-777991.

Drug: ACT-777991 (MAD); Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B3

EXPERIMENTAL

Multiple doses B3 of ACT-777991.

Drug: ACT-777991 (MAD); Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B4

EXPERIMENTAL

Multiple doses B4 of ACT-777991.

Drug: ACT-777991 (MAD); Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B5

EXPERIMENTAL

Multiple doses B5 of ACT-777991.

Drug: ACT-777991 (MAD); Drug: Placebo (MAD)

Part A (single ascending dose) Absolute Bioavailability

EXPERIMENTAL

Single dose of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from A4 to A8.

Drug: 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability); Drug: Microtracer matching placebo (SAD - Absolute Bioavailability)

Part B (multiple ascending dose) ADME

EXPERIMENTAL

Multiple doses of ACT-777991 plus a single dose of 14C-ACT-777991. At one of the dose levels from B1 to B5.

Drug: 14C-ACT-777991 microtracer (MAD - ADME); Drug: Microtracer matching placebo (MAD - ADME)

Interventions

ACT-777991 (SAD) DRUG

ACT-777991 administered as hard capsules for oral use.

Part A (single ascending dose arm) Dose A2; Part A (single ascending dose arm) Dose A3; Part A (single ascending dose arm) Dose A4; Part A (single ascending dose arm) Dose A5; Part A (single ascending dose arm) Dose A6; Part A (single ascending dose arm) Dose A7; Part A (single ascending dose arm) Dose A8; Part A (single ascending dose) Dose A1

ACT-777991 (MAD) DRUG

ACT-777991 administered as hard capsules for oral use, once daily.

Part B (multiple ascending dose) Dose B1; Part B (multiple ascending dose) Dose B2; Part B (multiple ascending dose) Dose B3; Part B (multiple ascending dose) Dose B4; Part B (multiple ascending dose) Dose B5

Placebo (SAD) DRUG

ACT-777991 matching placebo administered as hard capsules for oral use.

Part A (single ascending dose arm) Dose A2; Part A (single ascending dose arm) Dose A3; Part A (single ascending dose arm) Dose A4; Part A (single ascending dose arm) Dose A5; Part A (single ascending dose arm) Dose A6; Part A (single ascending dose arm) Dose A7; Part A (single ascending dose arm) Dose A8; Part A (single ascending dose) Dose A1

Placebo (MAD) DRUG

Matching placebo administered as hard capsules for oral use, once daily.

Part B (multiple ascending dose) Dose B1; Part B (multiple ascending dose) Dose B2; Part B (multiple ascending dose) Dose B3; Part B (multiple ascending dose) Dose B4; Part B (multiple ascending dose) Dose B5

14C-ACT-777991 microtracer (SAD - Absolute Bioavailability) DRUG

Single dose of 14C-ACT-777991 microtracer, administered intravenously.

Part A (single ascending dose) Absolute Bioavailability

Microtracer matching placebo (SAD - Absolute Bioavailability) DRUG

Single dose of 14C-ACT-777991 microtracer matching placebo, administered intravenously.

Part A (single ascending dose) Absolute Bioavailability

14C-ACT-777991 microtracer (MAD - ADME) DRUG

Single dose of 14C-ACT-777991 microtracer, oral solution..

Part B (multiple ascending dose) ADME

Microtracer matching placebo (MAD - ADME) DRUG

Single dose of 14C-ACT-777991 microtracer matching placebo, oral solution.

Part B (multiple ascending dose) ADME

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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 less than 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.

You may not qualify if:

• 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.
• Radiation exposure, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 milli sievert (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 Carbon-14 (14C) radiolabeled compound within the 12 months prior to Screening.
• Pregnant or lactating women.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

QPS Netherlands B.V.

Groningen, 9713 GZ, Netherlands

Location

MeSH Terms

Interventions

Sagittal Abdominal Diameter; mycophenolic adenine dinucleotide

Intervention Hierarchy (Ancestors)

Body Size; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Anthropometry; Investigative Techniques; Physiological Phenomena

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-center, double-blind, randomized, placebo-controlled Phase 1 study

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: March 15, 2021
• Study Start: January 29, 2021
• Primary Completion: January 26, 2022
• Study Completion: May 21, 2022
• Last Updated: June 21, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)