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

Idorsia Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04798209

ID-089-101

2020-004464-26 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 70 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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 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.

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 absorption,distribution, metabolism and excretion (ADME) evaluation:

• 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.

Exclusion Criteria for Part B:

• Pregnant or lactating women.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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70 participants in 15 patient groups

Part A (single ascending dose) Dose A1

Experimental group

Description:

Single dose A1 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A2

Experimental group

Description:

Single dose A2 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A3

Experimental group

Description:

Single dose A3 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A4

Experimental group

Description:

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

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A5

Experimental group

Description:

Single dose A5 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A6

Experimental group

Description:

Single dose A6 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A7

Experimental group

Description:

Single dose A7 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part A (single ascending dose arm) Dose A8

Experimental group

Description:

Single dose A8 of ACT-777991.

Treatment:

Drug: Placebo (SAD)

Drug: ACT-777991 (SAD)

Part B (multiple ascending dose) Dose B1

Experimental group

Description:

Multiple doses B1 of ACT-777991.

Treatment:

Drug: ACT-777991 (MAD)

Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B2

Experimental group

Description:

Multiple doses B2 of ACT-777991.

Treatment:

Drug: ACT-777991 (MAD)

Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B3

Experimental group

Description:

Multiple doses B3 of ACT-777991.

Treatment:

Drug: ACT-777991 (MAD)

Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B4

Experimental group

Description:

Multiple doses B4 of ACT-777991.

Treatment:

Drug: ACT-777991 (MAD)

Drug: Placebo (MAD)

Part B (multiple ascending dose) Dose B5

Experimental group

Description:

Multiple doses B5 of ACT-777991.

Treatment:

Drug: ACT-777991 (MAD)

Drug: Placebo (MAD)

Part A (single ascending dose) Absolute Bioavailability

Experimental group

Description:

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

Treatment:

Drug: 14C-ACT-777991 microtracer (SAD - Absolute Bioavailability)

Drug: Microtracer matching placebo (SAD - Absolute Bioavailability)

Part B (multiple ascending dose) ADME

Experimental group

Description:

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

Treatment:

Drug: Microtracer matching placebo (MAD - ADME)

Drug: 14C-ACT-777991 microtracer (MAD - ADME)