Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-389949 in Healthy Subjects

NCT ID: NCT02099201

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2013-05-31

Brief Summary

This is a single-center, double-blind, parallel-group, randomized, placebo-controlled, multiple-ascending oral dose study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT-389949 in healthy subjects.

Part A of the study will evaluate the safety and tolerability following once a day oral dosing of ACT-389949 for 9 days and investigate ACT-389949 pharmacokinetics and pharmacodynamics.

Part B of the study will evaluate the safety and tolerability of ACT-389949 following a maximum of two different oral dosing regimens: ACT-389949 given either every 3 days for 13 days or every 2 days for 9 days (5 doses for each regimen).

Part C of the study, if required, will provide additional information to that obtained from Parts A and B in terms of safety, tolerability, pharmacokinetics, and pharmacodynamics of ACT-389949.

Conditions

Healthy Subjects

Study Design

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

Study Groups

Group A1

Ten subjects will receive ACT-389949 40 mg and 3 subjects will receive placebo, once a day for 9 days Medication will be administered orally, in the morning, following an overnight fast.

Group Type: EXPERIMENTAL

ACT-389949 40 mg

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group A2

Ten subjects will receive ACT-389949 (Predicted to be 200 mg) and 3 subjects will receive placebo, once a day for 9 days Medication will be administered orally, in the morning, following an overnight fast.

Group Type: EXPERIMENTAL

ACT-389949 200 mg

Intervention Type: DRUG

Predicted dose

Placebo

Intervention Type: DRUG

Group A3

Ten subjects will receive ACT-389949 (Predicted to be 800 mg) and 3 subjects will receive placebo, once a day for 9 days Medication will be administered orally, in the morning, following an overnight fast.

Group Type: EXPERIMENTAL

ACT-389949 800 mg

Intervention Type: DRUG

Predicted dose

Placebo

Intervention Type: DRUG

Group B1

Ten subjects will receive ACT-389949 200 mg and 3 subjects will receive placebo, every 3 days for 13 days (a total of 5 doses), administered orally, in the morning, following an overnight fast.

Group Type: EXPERIMENTAL

ACT-389949 200 mg

Intervention Type: DRUG

Predicted dose

Placebo

Intervention Type: DRUG

Group B2

Ten subjects will receive ACT-389949 (provisionally 200 mg) and 3 subjects will receive placebo, every 2 days for 9 days (a total of 5 doses), administered orally, in the morning following an overnight fast. The actual dose will depend on the emerging data from Group B1.

Group Type: EXPERIMENTAL

ACT-389949 200 mg

Intervention Type: DRUG

Predicted dose

Placebo

Intervention Type: DRUG

Group C1

10 subjects will receive ACT-389949 and 3 subjects on placebo. The actual dose will depend on the emerging data from the previous groups but will be within the dose range or lower than the dose range tested in Part A. The dosing schedule will be one of those already tested in Part A and/or Part B.

Group Type: EXPERIMENTAL

ACT-389949 (Group C1 dose to be selected)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Group C2

10 subjects will receive ACT-389949 and 3 subjects on placebo. The actual dose will depend on the emerging data from the previous groups but will be within the dose range or lower than the dose range tested in Part A. The dosing schedule will be one of those already tested in Part A and/or Part B.

Group Type: EXPERIMENTAL

ACT-389949 (Group C2 dose to be selected)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Interventions

ACT-389949 40 mg

Intervention Type: DRUG

ACT-389949 200 mg

Predicted dose

Intervention Type: DRUG

ACT-389949 800 mg

Predicted dose

Intervention Type: DRUG

ACT-389949 (Group C1 dose to be selected)

Intervention Type: DRUG

ACT-389949 (Group C2 dose to be selected)

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent in local language.
• Healthy Caucasian male subjects and female subjects of non-childbearing potential.
• Men with female partners of childbearing potential must agree to use 2 reliable methods of contraception from first drug administration up to a minimum of 90 days after the end of treatment.
• Male subjects must agree not to donate sperm from the first drug administration until 90 days after the end of treatment.
• Non-smokers, defined as never smoked or achieved cessation ≥ 12 months prior to screening.
• Body mass index of 18.0 to 28.0 kg/m^2 (inclusive) at screening.
• No clinically significant findings on the physical examination at screening.
• Negative results from urine alcohol and drug screen at screening and on Day -1.
• Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive) measured at screening.
• 12-Lead electrocardiogram without clinically relevant abnormalities at screening.
• Body temperature 35.5-37.7 °C at screening and prior to first dosing.
• C-reactive protein (CRP) and total and differential white blood cell (WBC)count within the local laboratory normal ranges at screening and on Day -1.
• Hematology, coagulation, clinical chemistry, and urinalysis results (other than total differential WBC and CRP), not deviating to a clinically relevant extent from the normal local laboratory range(s) at screening.
• Forced expiratory volume in 1 second (FEV1) ≥ 80% of predicted, FEV1 / Forced vital capacity ≥ 70%.
• Subjects must be able to provide adequate sputum following induction with hypertonic saline at screening.
• Able to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
• Able to stay in the unit for the entire duration required and undertake all study related procedures.

Exclusion Criteria

• 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 might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous puncture on either arm.
• Loss of 250 mL or more of blood or blood donation, within 3 months prior to screening.
• Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s).
• Previous exposure to ACT-389949.
• Exposure to lipopolysaccharide within the last year.
• Treatment with another investigational drug within 3 months prior to screening or participation in more than 4 investigational drug studies within 1 year prior to screening.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Excessive caffeine consumption.
• Use of regular medication or therapy (including vaccines) or over-the-counter medications within 2 weeks prior to first study drug administration or 5 half-lives of the medication, whichever is longer.
• Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
• Positive results from the human immunodeficiency virus serology at screening.
• Vaccinations within the previous 6 months or foreign travel to areas within the last 6 months where infectious diseases are prevalent.
• Signs or symptoms suggestive of infection within 2 weeks prior to study screening and between screening and dosing.
• Signs of respiratory tract infections within 2 weeks prior to screening and between screening and dosing.
• History of atopic allergy.
• Hay fever, if within active season.
• Chronic diseases including those with recurring periods of flare-ups and remission.
• Legal incapacity or limited legal capacity at screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Idorsia Pharmaceuticals Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alison Mackie, MSc

Role: STUDY_DIRECTOR

Actelion

Locations

Celerion

Belfast, , United Kingdom

Countries

United Kingdom

Other Identifiers

AC-073-102

Identifier Type: -

Identifier Source: org_study_id