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

NCT ID: NCT02029482

Last Updated: 2014-01-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-06-30

Brief Summary

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.

Conditions

Safety and Tolerability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

ACT-128800

ACT-128800 tablets, once daily for 3 days at each dose level: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg, and 100 mg.

Group Type: EXPERIMENTAL

ACT-128800

Intervention Type: DRUG

Placebo

Matching placebo tablets, once daily, for 18 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

ACT-128800

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Darren Wilbraham, MBBS, DCPSA

Role: PRINCIPAL_INVESTIGATOR

Quintiles Drug Research Unit

Locations

Quintiles Drug Research Unit at Guy's Hospital

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

AC-058-109

Identifier Type: -

Identifier Source: org_study_id