Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-128800 in Healthy Subjects

Actelion Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Safety and Tolerability

Treatments

Drug: Placebo

Drug: ACT-128800

Study type

Interventional

Funder types

Industry

Identifiers

NCT02029482

AC-058-109

Details and patient eligibility

About

This was a single-center, randomized, double-blind, placebo-controlled, up-titration Phase 1 study. Sixteen subjects in two groups (at least 40% of subjects of either male or female sex), with 12 subjects in the active treatment group with an up-titration scheme from 10 to 100 mg, and 4 subjects in the placebo treatment group. Subjects were administered ascending doses of ACT-128800/placebo once daily for 3 days at each dose level: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg, and 100 mg.

Enrollment

16 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Signed informed consent in the local language prior to any study-mandated procedure.
Age between 18 and 65 years (inclusive) at screening.
Body mass index (BMI) between 18 and 30 kg/m^2 (inclusive).
Women of childbearing potential were required to have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to first drug intake and have agreed to use two methods of contraception from the screening visit until 2 months after study drug discontinuation.
Systolic blood pressure 100-150 mmHg, diastolic blood pressure 50-90 mmHg measured on the leading arm, and heart rate 50-95 beats per minute (inclusive) measured by electrocardiography (ECG) after 5 minutes in the supine position at screening.
ECG without clinically relevant abnormalities at screening.
Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
Negative results from urine drug screen at screening.
Ability to communicate well with the investigator and to understand and comply with the requirements of the study.

Exclusion criteria

ECG recording; PQ/PR interval > 200 ms at screening.
Pregnant or lactating women.
Known hypersensitivity to any excipients of the drug formulation.
Known hypersensitivity to beta2 adrenergic receptor agonists.
Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access or puncture; veins with a tendency to rupture during or after puncture).
Treatment with another investigational drug within 3 months prior to screening.
Excessive caffeine consumption, defined as ≥ 800 mg per day at screening. History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drug.
Smoking within the last month prior to screening.
Any immunosuppressive treatment within 6 weeks before study drug administration.
Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to screening or 5 half-lives of the drug, whichever is longer.
Loss of 250 mL or more of blood within 3 months prior to screening.
Lymphopenia (< 1,000 cells/μL).
Viral, fungal, bacterial or protozoal infection within 4 weeks before study drug administration (e.g., active herpes and/or cytomegalovirus infection).
History or clinical evidence suggestive of active or latent tuberculosis at screening.
Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
Positive results from the human immunodeficiency virus serology at screening.
Forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 80% of the predicted value, or FEV1/FVC ratio < 0.7 at screening.
History of asthma or chronic obstructive pulmonary disease.
Any cardiac condition or illness (including ECG abnormalities) with a potential to increase the cardiac risk of the subject in the standard 12-lead ECG and 24-hour 3-lead Holter ECG at screening.
History of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
Familial history of sick-sinus syndrome.
History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening. Alcohol abuse is defined as regular weekly intake of more than 21 units.
Legal incapacity or limited legal capacity at screening.
Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.