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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
Sponsored by
ObsEva SA
About
Eligibility
Locations
Arms
Outcomes
Full info

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

  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

Sites / Locations

  • Clinical Site
  • Clinical Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

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

First Posted
May 22, 2019
Last Updated
January 9, 2020
Sponsor
ObsEva SA
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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
No
Data Monitoring Committee
No

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
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
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
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)
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
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
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
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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