Safety and Pharmacokinetics Study of Linzagolix in Female Subjects With Normal and Impaired Hepatic Function

Healthy Participants Clinical Trial

Official title:

Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Hepatic Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03962049
• Other study ID #: 18-OBE2109-009
• Status: Completed
• Phase: Phase 1
• Start date: May 15, 2019
• Est. completion date: November 1, 2019

Study information

• Verified date: January 2020
• Source: ObsEva SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to assess the pharmacokinetics (PK) of linzagolix in subjects with varying degrees of impaired hepatic function compared to match control subjects with normal hepatic function

Description:

This is a Phase 1, non-randomized, open label, single-dose study to evaluate the effect of varying degrees of impaired hepatic function (i.e., mild, moderate, and severe Hepatic Impairment (HI)) on the PK, safety, and tolerability of linzagolix and its major metabolite, KP017.

Up to 28 adult female participants will be enrolled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 1, 2019
• Est. primary completion date: October 23, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

Hepatic Impaired Subjects

1. Adult female, 18-75 years of age, inclusive, at screening

2. Has a BMI = 18.0 and = 42.0 kg/m^2 and weight = 40 kg, at screening

3. Aside from HI, be sufficiently healthy for study participation based upon medical history, physical examination, vital signs, electrocardiograms (ECGs), and screening clinical laboratory profiles, as deemed by the Principal Investigator (PI) or designee

4. Has a score on the Child-Pugh scale at screening as follows:

• Severe HI: = 10 and = 15

• Moderate HI: = 7 and = 9

• Mild HI: = 5 and = 6

5. Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology

Healthy Subjects

1. Healthy adult female will be matched based upon age and BMI

2. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.

Key Exclusion Criteria:

Hepatic Impaired Subjects

1. Has a clinically active Grade 3 or 4 encephalopathy

2. Has fluctuating or rapidly deteriorating hepatic function within the screening period, and up to 30 days prior to Day 1, in the opinion of the PI and Sponsor

3. Has history of liver or other solid organ transplant

4. Had any major surgery within 4 weeks prior to dosing

5. Has a surgical (e.g., hepatectomy, nephrectomy, digestive organ resection) or medical condition other than HI which might significantly alter the absorption, distribution, metabolism, or excretion of linzagolix and its metabolites, or which may jeopardize the subject's safety in case of participation in the study in the opinion of the PI or designee

Healthy Subjects

1. Has any clinically significant illness, as judged by the PI or designee, within 4 weeks prior to dosing

2. Has laboratory values at screening or check-in which are deemed to be clinically significant (especially derangement within liver function test), unless agreed in advance by the PI and the Sponsor

Related Conditions & MeSH terms

• Healthy Participants
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• Linzagolix
A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions

Locations

Country	Name	City	State
United States	Clinical Site	Hialeah	Florida
United States	Clinical Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ObsEva SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017	Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the maximum plasma concentration (Cmax). Cmax directly determined from the plasma concentration-time profiles	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Primary	Plasma PK parameter Tmax of linzagolix and of KP017	Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Primary	Plasma PK parameter AUC0-t of linzagolix and of KP017	Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the AUC0-t (area under the concentration time curve, from time 0 to the last observed non-zero concentration)	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Primary	Plasma PK parameter T1/2 of linzagolix and of KP017	Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Secondary	Treatment emergent Adverse Events	Assessment of safety and tolerability of a single dose of linzagolix in hepatic impaired subjects compared with healthy control subjects by assessing the number, frequency and severity of treatment emergent Adverse Events	Day 1 to 14 days post-dose