The Effect of Reduced Liver Function on Selatogrel Pharmacokinetics

NCT04406896 | Completed Phase 1

• 2 other identifiers: ID-076-1082020-001315-25
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Healthy Subjects; Hepatic Impairment

Outcome Measures

Primary Outcomes (8)

• The maximum plasma concentration (Cmax) of selatogrel

  Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.

• Time to reach Cmax (tmax)

  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

  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

  Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.

• Terminal half-life (t½) of selatogrel

  Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.

• The apparent clearance (CL/F) of selatogrel

  Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.

• The apparent volume of distribution (Vz/F) of selatogrel

  Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.

• Plasma protein binding of selatogrel

  Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose and post-dose).

Secondary Outcomes (7)

• 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 in pulse rate

  Multiple predefined times on Day 1 (pre-dose) up to Day 3.

• 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.

Study Arms (3)

Participants with mild hepatic impairment (Group 1)

EXPERIMENTAL

Participant with Child-Pugh Grade A Score of 5-6.

Drug: Selatogrel

Participants with moderate hepatic impairment (Group 2)

EXPERIMENTAL

Participant with moderate hepatic impairment with a Child-Pugh Grade B Score of 7-9.

Drug: Selatogrel

Healthy participants (Group 3)

EXPERIMENTAL

Drug: Selatogrel

Interventions

Selatogrel DRUG

A single subcutaneous injection of 16 mg.

Also known as: ACT-246475

Healthy participants (Group 3); Participants with mild hepatic impairment (Group 1); Participants with moderate hepatic impairment (Group 2)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Hepatic impairment due to liver cirrhosis according to the Child-Pugh classification:
• Group 1: Mild hepatic impairment, Child-Pugh A = score 5-6.
• Group 2: Moderate hepatic impairment, Child-Pugh B = score 7-9.
• Systolic blood pressure (SBP) 95-160 mmHg, diastolic blood pressure (DBP) 60-95 mmHg, and pulse rate 50-100 bpm (inclusive), measured on the same arm, after 5 minutes in the supine position at screening and on Day 1 (pre-dose).
• Estimated glomerular filtration rate (eGFR) at screening using the Modification of Diet in Renal Disease (MDRD) formula of:
• greater than or equal to 60 mL/min/1.73 m2 for participants with mild hepatic impairment (Group 1)
• greater than or equal to 45 mL/min/1.73 m2 for participants with moderate hepatic impairment (Group 2).
• Stable concomitant medications for at least 3 weeks prior to screening and up to Day 1 and expected to be stable during the conduct of the study.
• Normal blood pressure measured on the same arm, after 5 minutes in the supine position at screening and on Day 1 pre-dose defined as:

You may not qualify if:

• 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.
• 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.
• Clinical evidence or suspected acute liver failure as judged by the investigator.
• Severe ascites and/or pleural effusion.
• Encephalopathy greater than grade 2.
• Clinical evidence of current alcohol or drug abuse.
• Clinically relevant abnormalities on a 12-lead ECG, except for abnormalities related to hepatic impairment, after 5 minutes in the supine position at screening and on Day 1 pre-dose.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition (e.g., cholecystectomy), which might interfere with the ADME of the study treatment (except for appendectomy and herniotomy).

Sponsors & Collaborators

• Viatris Innovation GmbH: lead

Study Sites (1)

CRS Clinical Research Services

Kiel, 24105, Germany

Location

MeSH Terms

Interventions

selatogrel

Study Officials

• Clinical Trials

  Viatris Innovation GmbH

  STUDY DIRECTOR

Study Design

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

Model Details: Moderate hepatic impaired participants will be dosed after an interim analysis of at least 6 participants with mild hepatic impairment. Healthy participants will be matched to hepatic impaired participants.

Study Record Dates

• First Submitted: May 25, 2020
• First Posted: May 29, 2020
• Study Start: July 22, 2020
• Primary Completion: October 23, 2020
• Study Completion: October 23, 2020
• Last Updated: July 4, 2025

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)