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.

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.

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.