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

Idorsia Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: ACT-389949 50 mg; Drug: ACT-389949 20 mg; Drug: ACT-389949 1 mg; Drug: ACT-389949 100 mg; Drug: Placebo; Drug: ACT-389949 1000 mg; Drug: ACT-389949 200 mg; Drug: ACT-389949 500 mg; Drug: ACT-389949 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02099071

AC-073-101

Details and patient eligibility

About

This is a prospective, single-center, double-blind, randomized, placebo-controlled, ascending single oral dose and food interaction Phase 1 study. It will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ascending single oral doses of ACT-389949 in healthy male subjects. It will also investigate the effect of food on the pharmacokinetics, safety, and tolerability of a single dose of ACT-389949.

Enrollment: 65 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Signed informed consent prior to any study-mandated procedure.
• Healthy Caucasian male subjects aged between 18 and 45 years (inclusive) at screening.
• Subjects must agree to use reliable methods of contraception.
• No clinically significant findings on physical examination at screening.
• Body mass index (BMI) between 18.0 and 30.0 kg/m^2 (inclusive) at screening.
• Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate (PR) 45-90 bpm (inclusive) measured at screening.
• 12-lead ECG without clinically relevant abnormalities, measured at screening.
• Body temperature (T°) 35.5-37.5°C at screening and prior to (first) dosing.
• Total and differential white blood cell (WBC) count strictly within the normal ranges at screening and on Day -1.
• C-reactive protein (CRP) levels below 5 mg/L.
• Hematology and clinical chemistry results (other than total and differential WBC count and CRP) not deviating from the normal range to a clinically relevant extent at screening.
• Coagulation and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
• Non smokers, defined as never smoked or achieved cessation for ≥ 6 months at screening.
• Negative results from urine drug screen at screening.
• Subjects allowing the conduct of genetic analyses on whole blood consisting of measuring the levels of messenger ribonucleic acid (mRNA) expression of mechanistic biomarkers of N-formyl-peptide receptor 2 (FPR2) and proteins involved in inflammation.
• Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.

Exclusion criteria

• Known allergic reactions or hypersensitivity to any excipient of the drug formulation.
• 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 recurrent fainting, collapses, syncope, orthostatic hypotension, or vasovagal reactions.
• Veins unsuitable for intravenous (i.v.) puncture on either arm.
• Treatment with another investigational drug within 3 months prior to screening or having participated in more than four 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.
• Treatment with any prescribed or over-the-counter (OTC) medications within 2 weeks prior to (first) study drug administration or five half-lives of the medication, whichever is longer.
• Any history of immunosuppressive treatment.
• Chronic diseases including those with recurring periods of flare-ups and remission.
• History of atopic allergy (including asthma, urticaria, eczematous dermatitis).
• Signs of infection (viral, systemic fungal, bacterial or protozoal) within 4 weeks prior to (first) study drug administration.
• History of acute or chronic obstructive lung disease (treated or not treated).
• History of subarachnoid hemorrhage or hemolytic uremic syndrome.
• Interval from the beginning of the P wave to the beginning of the QRS complex (PQ/PR interval) < 120 ms at screening.
• 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, at screening.
• Positive results from the human immunodeficiency virus serology at screening.
• 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 at screening.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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65 participants in 8 patient groups

Group 1

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 1 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: Placebo

Drug: ACT-389949 1 mg

Group 2

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 5 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: Placebo

Drug: ACT-389949 5 mg

Group 3

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 20 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: Placebo

Drug: ACT-389949 20 mg

Group 4

Experimental group

Description:

Subjects will participate in two different treatment periods separated by a washout of 7-10 days between the study drug administrations. In the first treatment period six subjects will receive a single oral dose of ACT-389949 50 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach. In the second treatment period, subjects randomized to ACT-389949 will receive a single oral dose of ACT-389949 50 mg in fed condition, 30 minutes after the start of a high fat and high calorie breakfast.

Treatment:

Drug: Placebo

Drug: ACT-389949 50 mg

Group 5

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 100 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: Placebo

Drug: ACT-389949 100 mg

Group 6

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 200 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: ACT-389949 200 mg

Drug: Placebo

Group 7

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 500 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: Placebo

Drug: ACT-389949 500 mg

Group 8

Experimental group

Description:

Six subjects will receive a single oral dose of ACT-389949 1000 mg and two subjects will receive a single oral dose of placebo. Treatment will be administered in the morning on an empty stomach.

Treatment:

Drug: Placebo

Drug: ACT-389949 1000 mg