A Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) and Ascending Multiple Doses of ACT-453859, and Multiple Doses of Setipiprant (ACT-129968)

NCT ID: NCT02381496

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2012-04-30

Brief Summary

This is a three-part study to assess the tolerability, safety, pharmacodynamics, and pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female subjects, and of multiple doses of setipiprant (ACT-129968) in healthy male and female subjects.

Detailed Description

Part A of this study is a single-center, randomized, double-blind, placebo-controlled, single-ascending dose (SAD) design in healthy male subjects. In each cohort, eight subjects will be randomized as follows:

• Six male subjects will receive a single oral dose of ACT-453859, under fasted conditions.
• Two male subjects will receive matching placebo, under fasted conditions.

The doses of ACT-453859 were 1, 3, 10, 30, 100, 300, and 800 mg. Subjects in only one cohort (100 mg dose cohort) will come back for a second period of treatment under fed conditions.

Part B is a single-center, randomized, double-blind, placebo-controlled multiple-ascending dose (MAD) design in healthy male and female of subjects.

In each of 3 cohorts, eight subjects will be randomized to receive multiple doses of ACT-453859 or placebo once a day for 7 days as follows:

• Three male subjects will receive ACT-453859.
• Three female subjects will receive ACT-453859.
• One male subject will receive matching placebo.
• One female subject will receive matching placebo.

The doses of ACT-453859 will be 10, 100, and 800 mg per day.

Part C is a single-center and open-label design consisting of multiple oral doses of setipiprant given in a sequential design in healthy male and female subjects.

Eight subjects will be randomized to receive multiple doses of setipiprant for 7 days (only a single dose on Day 7), in Treatment Period I (TPI) and Treatment Period II (TPII), as follows:

• Four male subjects will receive setipiprant 500 mg twice a day (b.i.d.) in TPI and 1000 mg b.i.d. in TPII.
• Four female subjects will receive setipiprant 500 mg b.i.d. in TPI and 1000 mg b.i.d. in TPII.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Part A: Cohort A1: ACT-453859 1 mg

ACT-453859 1 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 1 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part A: Cohort A2: ACT-453859 3 mg

ACT-453859 3 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 3 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part A: Cohort A3: ACT-453859 10 mg

ACT-453859 10 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 10 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part A: Cohort A4: ACT-453859 30 mg

ACT-453859 30 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 30mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part A: Cohort A5: ACT-453859 100 mg

ACT-453859 100 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

After a washout period of 10-20 days subjects will return for a second study period to receive the same treatment received in the first session but under fed conditions

Group Type: EXPERIMENTAL

ACT-453859 100 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part A: Cohort A6: ACT-453859 300 mg

ACT-453859 300 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 300 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part A: Cohort A7: ACT-453859 800 mg

ACT-453859 800 mg or placebo, single dose, administered orally in the fasted state

• Six male subjects will receive ACT-453859
• Two male subjects will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 800 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part B: Cohort B1: ACT-453859 10 mg

ACT-453859 10 mg or placebo, once a day for 7 days, administered orally in the fasted state

• Three male subjects will receive ACT-453859
• Three female subjects will receive ACT-453859
• One male subject will receive matching placebo
• One female subject will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 10 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part B: Cohort B2: ACT-453859 100 mg

ACT-453859 100 mg or placebo, once a day for 7 days, administered orally in the fasted state

• Three male subjects will receive ACT-453859
• Three female subjects will receive ACT-453859
• One male subject will receive matching placebo
• One female subject will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 100 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part B: Cohort B3: ACT-453859 800 mg

ACT-453859 800 mg, once a day for 7 days, administered orally in the fasted state

• Three male subjects will receive ACT-453859
• Three female subjects will receive ACT-453859
• One male subject will receive matching placebo
• One female subject will receive matching placebo

Group Type: EXPERIMENTAL

ACT-453859 800 mg

Intervention Type: DRUG

Capsule

Placebo

Intervention Type: OTHER

Matching ACT-453859 placebo capsule

Part C: Treatment Periods I & II: Setipiprant

Setipiprant 500 mg, twice daily for 7 days, administered orally in Treatment Period I (TPI) and setipiprant 1000 mg, twice daily for 7 days, administered orally in Treatment Period II (TPII)

• Four male subjects will receive setipiprant 500 mg twice a day in TPI and 1000 mg twice a day in TPII.
• Four female subjects will receive setipiprant 500 mg twice a day in TPI and 1000 mg twice a day in TPII.

There will be a washout period of 10 days between TPI and TPII

Group Type: EXPERIMENTAL

Setipiprant 500 mg

Intervention Type: DRUG

Capsule

Setipiprant 1000 mg

Intervention Type: DRUG

Capsule

Interventions

ACT-453859 1 mg

Capsule

Intervention Type: DRUG

ACT-453859 3 mg

Capsule

Intervention Type: DRUG

ACT-453859 10 mg

Capsule

Intervention Type: DRUG

ACT-453859 30mg

Capsule

Intervention Type: DRUG

ACT-453859 100 mg

Capsule

Intervention Type: DRUG

ACT-453859 300 mg

Capsule

Intervention Type: DRUG

ACT-453859 800 mg

Capsule

Intervention Type: DRUG

Placebo

Matching ACT-453859 placebo capsule

Intervention Type: OTHER

Setipiprant 500 mg

Capsule

Intervention Type: DRUG

Setipiprant 1000 mg

Capsule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent.
• Healthy male subjects (Part A), healthy male and female subjects for Parts B & C.
• Hematology, coagulation (Part A and Part B only), clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent.
• No clinically significant findings on physical examination.
• Body mass index between 18.0 and 28.0 kg/m^2.
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and heart rate 45-90 beats per minute.
• 12-lead electrocardiogram without clinically relevant abnormalities.
• Negative results from urine drug screen and alcohol breath test.
• Able and willing to refrain from sunbathing, prolonged sun exposure, and artificial sunlight exposure such as solarium, and to limit skin and eye exposure to sunlight using appropriate precautions from the first dose until safety follow-up visit for Parts A and B.
• Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
• For male subjects: consent that the female partner uses a medically acceptable method of contraception throughout the entire study period and for 90 days after the study is completed.
• For male subjects: agree not to donate sperm from the first drug administration until 90 days after completion of the study.
• For Part C, women of childbearing potential must have a negative serum pregnancy test and a negative urine pregnancy test pre-dose on Day 1 (of each treatment period for Part C). Women of childbearing potential must consistently and correctly use a reliable method of contraception, be sexually inactive or have a vasectomized partner.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

• Previous history of fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous puncture on either arm.
• Treatment with any prescribed or over-the-counter medications within 2 weeks prior to first study drug administration.
• Treatment or substances known to inhibit cytochrome P (CYP) enzyme drug metabolism .
• Treatment or substances known to induce CYP enzyme drug metabolism.
• Treatment with another investigational drug within 3 months prior or participated in more than four investigational drug studies within 1 year prior to Screening. Subjects will not participate in more than one part of the study.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to Screening.
• 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 drugs.
• Excessive caffeine consumption.
• Smoking, tobacco use, or use of nicotine products within 3 months and inability to refrain from smoking during the course of the study.
• Loss of 250 mL or more of blood, or an equivalent amount of plasma, within 3 months prior to Screening.
• Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis.
• Positive results from human immunodeficiency virus serology.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity.
• Pregnant or lactating women.
• Known allergic reactions or hypersensitivity to any excipients of the drug formulations.
• Difficulty in fasting or consuming standardized meals.
• Difficulty in swallowing whole tablets or capsules.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martine Géhin, PhD

Role: STUDY_DIRECTOR

Actelion

Other Identifiers

AC-072-101

Identifier Type: -

Identifier Source: org_study_id