An Open-label, Single-dose, Phase 1 Study to Evaluate the Pharmacokinetics of Selatogrel in Subjects With Mild and Moderate Hepatic Impairment Compared to Matched Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- Selatogrel
- Conditions
- Healthy Subjects
- Sponsor
- Viatris Innovation GmbH
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Plasma protein binding of selatogrel
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This is a prospective, single-center, open-label, single-dose, Phase 1 study, to assess the effect of mild and moderate hepatic impairment due to liver cirrhosis on the pharmacokinetics of selatogrel (ACT-246475).
Investigators
Eligibility Criteria
Inclusion Criteria
- •All participants (Groups 1,2 and 3)
- •Signed informed consent in a language understandable to the participant prior to any study-mandated procedure.
- •Male or female participant aged between 18 and 79 years (inclusive) at screening.
- •Body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening.
- •Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 (pre-dose). They must consistently and correctly use (from screening, during the entire study, and for at least 30 days after last study treatment administration) an acceptable effective method of contraception method, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must have been initiated at least 1 month before treatment administration.
- •Women of non-childbearing potential.
- •Additional principal inclusion criteria for participants with hepatic impairment (Groups 1 and 2)
- •Hepatic impairment due to liver cirrhosis according to the Child-Pugh classification:
- •Group 1: Mild hepatic impairment, Child-Pugh A = score 5-
- •Group 2: Moderate hepatic impairment, Child-Pugh B = score 7-
Exclusion Criteria
- •All participants (Groups 1, 2 and 3)
- •Pregnant or lactating woman.
- •Previous exposure to selatogrel.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- •Known hypersensitivity to P2Y12 receptor antagonists or any excipients of the drug formulation.
- •Known platelet disorders.
- •Legal incapacity or limited legal capacity at screening.
- •Additional exclusion criteria for participants with hepatic impairment (Groups 1 and 2)
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition (e.g., cholecystectomy), which might interfere with the absorption, distribution, metabolism, and excretion (ADME) of the study treatment (except for hepatic impairment, appendectomy, and herniotomy).
- •Acute hepatitis, hepatic cancer, primary biliary cirrhosis, or any form of cholestatic disease.
Arms & Interventions
Participants with mild hepatic impairment (Group 1)
Participant with Child-Pugh Grade A Score of 5-6.
Intervention: Selatogrel
Participants with moderate hepatic impairment (Group 2)
Participant with moderate hepatic impairment with a Child-Pugh Grade B Score of 7-9.
Intervention: Selatogrel
Healthy participants (Group 3)
Intervention: Selatogrel
Outcomes
Primary Outcomes
Plasma protein binding of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose and post-dose).
The maximum plasma concentration (Cmax) of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
The apparent volume of distribution (Vz/F) of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Area under the plasma concentration-time curves (AUC0-t) of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
The area under the plasma concentration-time curve from zero to infinity (AUC0-inf) of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
The apparent clearance (CL/F) of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Terminal half-life (t½) of selatogrel
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Time to reach Cmax (tmax)
Time Frame: Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Secondary Outcomes
- Change from baseline in body weight(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)
- Change from baseline in clinical laboratory tests(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)
- Change from baseline in pulse rate(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)
- Change from baseline in supine blood pressure(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)
- Change from baseline in temperature(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)
- Change from baseline at each time point of measurement in ECG variables.(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)
- Inhibition of platelet aggregation(Multiple predefined times on Day 1 (pre-dose) up to Day 3.)