Clinical trial NCT01877629: Clinical Study to Assess the Pharmacokinetics, Safety, and Tolerability of ACT-129968 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Pharmacokinetics
Tolerability
Safety
ACT-129968
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2013-06-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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).
timeFrame: Up to 48 h in each treatment period (1 and 2)
measure: The area under the plasma concentration-time curve from zero to infinity (AUC0-infinity).
timeFrame: Up to 48 h in each treatment period (1 and 2)
measure: The maximum plasma concentration (Cmax)
timeFrame: Up to 48 h in each treatment period (1 and 2)
measure: The time to reach maximum plasma concentration (tmax)
timeFrame: Up to 48 h in each treatment period (1 and 2)
measure: The terminal elimination half-life (t½)
timeFrame: Up to 48 h in each treatment period (1 and 2)
Secondary outcomes:
measure: Change from baseline to each time point of measurement during each treatment period and to EOS in supine blood pressure
timeFrame: Up to 13 days
measure: Change from baseline to each time point of measurement during each treatment period and to EOS in pulse rate
timeFrame: Up to 13 days
measure: Body weight at baseline and end of study visit
timeFrame: Up to 13 days
measure: Change from baseline to EOS for hematology
timeFrame: Up to 13 days
measure: Change from baseline to EOS for clinical chemistry
timeFrame: Up to 13 days
measure: Change from baseline to EOS for pregnancy serum test
timeFrame: Up to 13 days
measure: Change from baseline to EOS for virus serology
timeFrame: Up to 13 days
measure: Change from baseline to each time point of measurement during each treatment period and to EOS in ECG variables
timeFrame: Up to 13 days
measure: Number of patients with treatment-emergent ECG abnormalities for each treatment period
timeFrame: from study drug administration on Day 1 up to 48 hours post-dose
measure: Number of patients with treatment-emergent physical examination abnormalities at EOS
timeFrame: Up to 13 days
measure: Number of patients with treatment-emergent AEs and SAEs for each treatment period
timeFrame: from study drug administration on Day 1 up to 48 hours post-dose
measure: Number of patients with AEs leading to premature discontinuation of study drug
timeFrame: Entire duration of study
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: PHAROS GmbH Clinical Research
Study officials:
affiliation: Actelion
name: Daniela Baldoni, PharmD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.