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

Primary Purpose

Hepatic Impairment, Healthy Participants

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Linzagolix

About this trial

This is an interventional basic science trial for Hepatic Impairment focused on measuring Linzagolix, OBE2109, Hepatic Impairment, Hepatic Insufficiency, Liver Diseases, Clinical pharmacology study

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Key Inclusion Criteria:

Hepatic Impaired Subjects

Adult female, 18-75 years of age, inclusive, at screening
Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening
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
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
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

Healthy adult female will be matched based upon age and BMI
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

Has a clinically active Grade 3 or 4 encephalopathy
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
Has history of liver or other solid organ transplant
Had any major surgery within 4 weeks prior to dosing
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

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

Sites / Locations

Clinical Site
Clinical Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Normal Hepatic Function

Mild Hepatic Impairment

Moderate Hepatic Impairment

Severe Hepatic Impairment

Arm Description

Healthy participants with Normal Hepatic Function

Presence of Mild Hepatic Impairment (score of 5 to 6, on the Child Pugh scale and with features of cirrhosis due to any etiology)

Presence of Moderate Hepatic Impairment (score of 7 to 9, on the Child Pugh scale and with features of cirrhosis due to any etiology)

Presence of Severe Hepatic Impairment (score of 10 to 15 on the Child Pugh scale and with features of cirrhosis due to any etiology)

Outcomes

Primary Outcome Measures

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

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)

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)

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)

Secondary Outcome Measures

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

Full Information

NCT ID

NCT03962049

First Posted

May 22, 2019

Last Updated

January 9, 2020

Sponsor

ObsEva SA

1. Study Identification

Unique Protocol Identification Number

NCT03962049

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2020

Overall Recruitment Status

Completed

Study Start Date

May 15, 2019 (Actual)

Primary Completion Date

October 23, 2019 (Actual)

Study Completion Date

November 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ObsEva SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Impairment, Healthy Participants

Keywords

Linzagolix, OBE2109, Hepatic Impairment, Hepatic Insufficiency, Liver Diseases, Clinical pharmacology study

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Hepatic Function

Arm Type

Experimental

Arm Description

Healthy participants with Normal Hepatic Function

Arm Title

Mild Hepatic Impairment

Arm Type

Experimental

Arm Description

Presence of Mild Hepatic Impairment (score of 5 to 6, on the Child Pugh scale and with features of cirrhosis due to any etiology)

Arm Title

Moderate Hepatic Impairment

Arm Type

Experimental

Arm Description

Presence of Moderate Hepatic Impairment (score of 7 to 9, on the Child Pugh scale and with features of cirrhosis due to any etiology)

Arm Title

Severe Hepatic Impairment

Arm Type

Experimental

Arm Description

Presence of Severe Hepatic Impairment (score of 10 to 15 on the Child Pugh scale and with features of cirrhosis due to any etiology)

Intervention Type

Drug

Intervention Name(s)

Linzagolix

Intervention Description

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

Primary Outcome Measure Information:

Title

Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017

Description

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Title

Plasma PK parameter Tmax of linzagolix and of KP017

Description

Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Title

Plasma PK parameter AUC0-t of linzagolix and of KP017

Description

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Title

Plasma PK parameter T1/2 of linzagolix and of KP017

Description

Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Secondary Outcome Measure Information:

Title

Treatment emergent Adverse Events

Description

Time Frame

Day 1 to 14 days post-dose

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Hepatic Impaired Subjects Adult female, 18-75 years of age, inclusive, at screening Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening 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 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 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 Healthy adult female will be matched based upon age and BMI 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 Has a clinically active Grade 3 or 4 encephalopathy 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 Has history of liver or other solid organ transplant Had any major surgery within 4 weeks prior to dosing 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 Has any clinically significant illness, as judged by the PI or designee, within 4 weeks prior to dosing 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

ObsEva SA

Organizational Affiliation

Geneva

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Site

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33014

Country

United States

Facility Name

Clinical Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

12. IPD Sharing Statement

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

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