Clinical Study to Assess the Pharmacokinetics, Safety, and Tolerability of ACT-129968 in Healthy Subjects

NCT01877629 | Completed Phase 1

• 1 other identifier: AC-060-104
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the pharmacokinetics (PK) of a single dose of two different formulations of ACT-129968, i.e., tablet versus capsule and to evaluate the safety and tolerability of a single dose of two different formulations of ACT-129968, i.e., tablet versus capsule.

Conditions

Healthy Subjects

Keywords

Pharmacokinetics; Tolerability; Safety; ACT-129968

Outcome Measures

Primary Outcomes (5)

• The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t).

  The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.

  Up to 48 h in each treatment period (1 and 2)

• The area under the plasma concentration-time curve from zero to infinity (AUC0-infinity).

  The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.

  Up to 48 h in each treatment period (1 and 2)

• The maximum plasma concentration (Cmax)

  The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.

  Up to 48 h in each treatment period (1 and 2)

• The time to reach maximum plasma concentration (tmax)

  The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.

  Up to 48 h in each treatment period (1 and 2)

• The terminal elimination half-life (t½)

  The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.

  Up to 48 h in each treatment period (1 and 2)

Secondary Outcomes (12)

• Change from baseline to each time point of measurement during each treatment period and to EOS in supine blood pressure

  Up to 13 days

• Change from baseline to each time point of measurement during each treatment period and to EOS in pulse rate

  Up to 13 days

• Body weight at baseline and end of study visit

  Up to 13 days

• Change from baseline to EOS for hematology

  Up to 13 days

• Change from baseline to EOS for clinical chemistry

  Up to 13 days

Study Arms (2)

ACT-129968 tablet/capsules

EXPERIMENTAL

Subjects attend two treatment periods. In the first treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as a tablet (1 tablet, 500 mg) in the fasted state. In the second treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as capsules (2 capsules, 250 mg each) in the fasted state. There is a 7-9 day washout period between the first treatment period and the second treatment period.

Drug: ACT-129968 500 mg tablet; Drug: ACT-129968 250 mg capsule

ACT-129968 capsules/tablet

EXPERIMENTAL

Subjects attend two treatment periods. In the first treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as capsules (2 capsules, 250 mg each) in the fasted state. In the second treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as a tablet (1 tablet, 500 mg each) in the fasted state. There is a 7-9 day washout period between the first treatment period and the second treatment period.

Drug: ACT-129968 500 mg tablet; Drug: ACT-129968 250 mg capsule

Interventions

ACT-129968 500 mg tablet DRUG

ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist

ACT-129968 capsules/tablet; ACT-129968 tablet/capsules

ACT-129968 250 mg capsule DRUG

ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist

ACT-129968 capsules/tablet; ACT-129968 tablet/capsules

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent in the local language prior to any study-mandated procedure.
• Women must have
• a negative serum pregnancy test at screening and
• a negative urine pregnancy test pre-dose on Day-1 of each treatment period.
• Women of childbearing potential must consistently and correctly use (from screening, during the entire study, and for at least 28 days after last study drug intake) a reliable method of contraception with a failure rate of \< 1% per year, be sexually inactive, or have a vasectomized partner.
• Women not of childbearing potential are defined as post-menopausal (i.e., spontaneous amenorrhea for at least 1 year without an alternative medical cause) or surgically or naturally sterile.
• No clinically significant findings on the physical examination at screening.
• Body mass index (BMI) of 18.0 to 28.0 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 on the dominant arm (dominant arm = writing arm) after 5 minutes in the supine position at screening.
• lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after 5 minutes in the supine position at screening.
• Hematology, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
• Negative results from urine drug screen and breath alcohol test at screening and on admission to the unit (Day-1) in Period 1 and Period 2.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

You may not qualify if:

• Pregnant or lactating women.
• Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s).
• 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 (appendectomy and herniotomy allowed, cholecystectomy not allowed).
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• History or clinical evidence of allergic rhinitis or asthma.
• 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).
• Previous exposure to the study medication.
• Treatment with another investigational drug within 3 months prior to screening or participation 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, defined as 800 mg per day at screening.
• Alcohol consumption of \> 21 units/week or \> 3 units/day.
• Smoking within 3 months prior to screening.
• Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to first study drug administration.
• Loss of 250 mL or more of blood within 3 months prior to screening.
• Positive results from the hepatitis serology (Hepatitis B surface antigen and anti-hepatitis C virus), except for vaccinated subjects or subjects with past but resolved hepatitis (defined as positive finding for antibodies but negative findings for antigens), at screening.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

PHAROS GmbH Clinical Research

Ulm, D-89081, Germany

Location

Related Publications (1)

• Baldoni D, Mackie A, Gutierrez M, Theodor R, Dingemanse J. Setipiprant, a selective oral antagonist of human CRTH2: relative bioavailability of a capsule and a tablet formulation in healthy female and male subjects. Clin Ther. 2013 Nov;35(11):1842-8. doi: 10.1016/j.clinthera.2013.09.003. Epub 2013 Oct 4.

  PMID: 24095247 DERIVED

MeSH Terms

Interventions

2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido(4,3-b)indol-5(2H)-yl)acetic acid; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Daniela Baldoni, PharmD, PhD

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 14, 2013
• Study Start: July 1, 2011
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

DE (1)