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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment; Healthy Participants
• Intervention / Treatment: Drug: Linzagolix

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hialeah, Florida, United States, 33014
      • Clinical Site
    • Orlando, Florida, United States, 32809
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Hepatic Function; Healthy participants with Normal Hepatic Function	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: Mild Hepatic Impairment; Presence of Mild Hepatic Impairment (score of 5 to 6, on the Child Pugh scale and with features of cirrhosis due to any etiology)	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: Moderate Hepatic Impairment; Presence of Moderate Hepatic Impairment (score of 7 to 9, on the Child Pugh scale and with features of cirrhosis due to any etiology)	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: Severe Hepatic Impairment; Presence of Severe Hepatic Impairment (score of 10 to 15 on the Child Pugh scale and with features of cirrhosis due to any etiology)	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: ObsEva SA
• Investigators: Study Director: ObsEva SA, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): October 23, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: May 22, 2019
• First Submitted That Met QC Criteria: May 22, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Liver Diseases; Hepatic Impairment; Clinical pharmacology study; Hepatic Insufficiency; Linzagolix; OBE2109
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 18-OBE2109-009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No