The Effect of Reduced Liver Function on Selatogrel Pharmacokinetics

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04406896
• Other study ID #: ID-076-108
• Secondary ID: 2020-001315-25
• Status: Completed
• Phase: Phase 1
• Start date: July 22, 2020
• Est. completion date: October 23, 2020

Study information

• Verified date: November 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 23, 2020
• Est. primary completion date: October 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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 5-6.

• 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.

Additional principal inclusion criteria for healthy participants (Group 3)

• 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:

• SBP 90 to 140 mmHg, DBP 60 to 90 mmHg, and pulse rate 50 to 100 bpm (inclusive) for participants less than 60 years of age.

• SBP 95 to 160 mmHg, DBP 65 to 95 mmHg, and pulse rate 50 to 100 bpm (inclusive) for participants 60 years and older.

• eGFR greater than or equal to 80 mL/min/1.73 m2 at screening using the MDRD formula.

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.

• 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.

Additional exclusion criteria for healthy participants (Group 3)

• 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).

• History or clinical evidence of alcohol or drug abuse within the 3 years prior to screening.

• Family or personal history of prolonged bleeding or bleeding disorders, intracranial vascular diseases, stroke, reasonable suspicion of vascular malformations, or peptic ulcers.

• Previous treatment with any prescribed medications or over-the-counter medications within 2 weeks or 5 times the terminal half-life (t½), whichever is longer prior to study treatment administration (excludes contraceptives and hormone replacement therapy).

Related Conditions & MeSH terms

• Healthy Subjects
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Selatogrel
A single subcutaneous injection of 16 mg.

Locations

Country	Name	City	State
Germany	CRS Clinical Research Services	Kiel

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The maximum plasma concentration (Cmax) of selatogrel		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Primary	Time to reach Cmax (tmax)		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Primary	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.
Primary	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.
Primary	Terminal half-life (t½) of selatogrel		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Primary	The apparent clearance (CL/F) of selatogrel		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Primary	The apparent volume of distribution (Vz/F) of selatogrel		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose) up to Day 3.
Primary	Plasma protein binding of selatogrel		Multiple pharmacokinetic sampling at predefined times on Day 1 (pre-dose and post-dose).
Secondary	Change from baseline in supine blood pressure		Multiple predefined times on Day 1 (pre-dose) up to Day 3.
Secondary	Change from baseline in temperature		Multiple predefined times on Day 1 (pre-dose) up to Day 3.
Secondary	Change from baseline in pulse rate		Multiple predefined times on Day 1 (pre-dose) up to Day 3.
Secondary	Change from baseline in body weight		Multiple predefined times on Day 1 (pre-dose) up to Day 3.
Secondary	Change from baseline in clinical laboratory tests		Multiple predefined times on Day 1 (pre-dose) up to Day 3.
Secondary	Change from baseline at each time point of measurement in ECG variables.		Multiple predefined times on Day 1 (pre-dose) up to Day 3.
Secondary	Inhibition of platelet aggregation		Multiple predefined times on Day 1 (pre-dose) up to Day 3.