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

Phase 1

Completed

• Conditions: Healthy Participants; Hepatic Impairment
• Interventions: Drug: Linzagolix

• Registration Number: NCT03962049
• Lead Sponsor: ObsEva SA

Brief 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

Detailed 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.

Study Timeline

• Study Start: 2019-05-15
• Study First Submitted: 2019-05-22
• Study First Submitted QC: 2019-05-22
• Study First Posted: 2019-05-23
• Primary Completion: 2019-10-23
• Study Completion: 2019-11-01
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-09
• Last Update Posted: 2020-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe Hepatic Impairment	Linzagolix	Presence of Severe Hepatic Impairment (score of 10 to 15 on the Child Pugh scale and with features of cirrhosis due to any etiology)
Mild Hepatic Impairment	Linzagolix	Presence of Mild Hepatic Impairment (score of 5 to 6, on the Child Pugh scale and with features of cirrhosis due to any etiology)
Normal Hepatic Function	Linzagolix	Healthy participants with Normal Hepatic Function
Moderate Hepatic Impairment	Linzagolix	Presence of Moderate Hepatic Impairment (score of 7 to 9, on the Child Pugh scale and with features of cirrhosis due to any etiology)

Primary Outcome Measures

Name	Time	Method
Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose	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
Plasma PK parameter Tmax of linzagolix and of KP017	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose	Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)
Plasma PK parameter AUC0-t of linzagolix and of KP017	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose	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)
Plasma PK parameter T1/2 of linzagolix and of KP017	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose	Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)

Secondary Outcome Measures

Name	Time	Method
Treatment emergent Adverse Events	Day 1 to 14 days post-dose	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

Trial Locations

Locations (1)

Clinical Site; 🇺🇸 Orlando, Florida, United States