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

NCT02029482 | Completed Phase 1

• 1 other identifier: AC-058-109
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Keywords

ACT-128800

Outcome Measures

Primary Outcomes (4)

• Change from baseline to Day 18 in systolic blood pressure

  Blood pressure was measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm right = writing with right hand). Measurements were recorded from the subject in the supine position after having rested for a 5-minute period.

  18 days

• Change from baseline to Day 18 in diastolic blood pressure

  Blood pressure was measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm right = writing with right hand). Measurements were recorded from the subject in the supine position after having rested for a 5-minute period.

  18 days

• Change from baseline to Day 18 in pulse rate

  Pulse rate was measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm right = writing with right hand). Measurements were recorded from the subject in the supine position after having rested for a 5-minute period.

  18 days

• Change from baseline to Day 18 in body temperature

  Body temperature was measured in the supine position using the same thermometer throughout the study.

  18 days

Secondary Outcomes (23)

• Change from baseline to Day 10 in mean absolute lymphocyte count

  10 days

• Change from baseline to Day 10 in mean T cell (Cluster of differentiation (CD) CD3+) lymphocyte count

  10 days

• Change from baseline to Day 10 in mean B cell (CD3-/CD19+) lymphocyte count

  10 days

• Change from baseline to Day 10 in mean natural killer (NK) cell (CD3-/CD56+) lymphocyte count

  10 days

• Change from baseline to Day 10 in mean natural killer T (NKT) cell (CD3+/CD56+) lymphocyte count

  10 days

Study Arms (2)

ACT-128800

EXPERIMENTAL

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.

Drug: ACT-128800

Placebo

PLACEBO COMPARATOR

Matching placebo tablets, once daily, for 18 days

Drug: Placebo

Interventions

ACT-128800 DRUG

ACT-128800

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Quintiles Drug Research Unit at Guy's Hospital

London, SE1 1YR, United Kingdom

Location

MeSH Terms

Interventions

ponesimod

Study Officials

• Darren Wilbraham, MBBS, DCPSA

  Quintiles Drug Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2014
• First Posted: January 8, 2014
• Study Start: April 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: January 8, 2014

Record last verified: 2014-01

Locations

GB (1)