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

A Single-center, Open-label, Two-period, Two-treatment, Crossover, Single-dose Study in Healthy Female and Male Subjects to Assess the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of ACT-129968

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: ACT-129968 500 mg tablet; Drug: ACT-129968 250 mg capsule

Detailed Description

A total of 10 female and 10 male healthy subjects will be enrolled and will attend two treatment periods, separated by a 7-9 day washout. Over these two periods, two formulations of ACT-129968 (Treatment A: two capsules, 250 mg each; Treatment B: one tablet, 500 mg) will be administered in the sequence A/B or B/A to 10 subjects (5 females and 5 males) per sequence as determined by randomization.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Ulm, Germany, D-89081
    • PHAROS GmbH Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.
• 12-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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACT-129968 tablet/capsules; 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; ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist; Drug: ACT-129968 250 mg capsule; ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist
Experimental: ACT-129968 capsules/tablet; 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; ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist; Drug: ACT-129968 250 mg capsule; ACT-129968, a tetrahydropyridoindole derivative, is a chemoattractant receptor homologous molecule expressed on T helper 2 cells (CRTH2) antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to each time point of measurement during each treatment period and to EOS in supine blood pressure	mmHg	Up to 13 days
Change from baseline to each time point of measurement during each treatment period and to EOS in pulse rate	bpm	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
Change from baseline to EOS for pregnancy serum test		Up to 13 days
Change from baseline to EOS for virus serology		Up to 13 days
Change from baseline to each time point of measurement during each treatment period and to EOS in ECG variables	ECG variables are to be recorded at rest using a standard 12-lead ECG	Up to 13 days
Number of patients with treatment-emergent ECG abnormalities for each treatment period		from study drug administration on Day 1 up to 48 hours post-dose
Number of patients with treatment-emergent physical examination abnormalities at EOS		Up to 13 days
Number of patients with treatment-emergent AEs and SAEs for each treatment period		from study drug administration on Day 1 up to 48 hours post-dose
Number of patients with AEs leading to premature discontinuation of study drug		Entire duration of study

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: June 13, 2013
• First Posted (Estimate): June 14, 2013

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: July 6, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Tolerability; ACT-129968
• Other Study ID Numbers: AC-060-104