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

NCT03962049 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-OBE2109-009
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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

Conditions

Hepatic Impairment; Healthy Participants

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Treatment emergent Adverse Events

  Day 1 to 14 days post-dose

Study Arms (4)

Normal Hepatic Function

EXPERIMENTAL

Healthy participants with Normal Hepatic Function

Drug: Linzagolix

Mild Hepatic Impairment

EXPERIMENTAL

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

Moderate Hepatic Impairment

EXPERIMENTAL

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

Severe Hepatic Impairment

EXPERIMENTAL

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

Interventions

Linzagolix DRUG

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

Mild Hepatic Impairment; Moderate Hepatic Impairment; Normal Hepatic Function; Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ObsEva SA: lead

Study Sites (2)

Clinical Site

Hialeah, Florida, 33014, United States

Location

Clinical Site

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Hepatic Insufficiency; Liver Diseases

Interventions

linzagolix

Condition Hierarchy (Ancestors)

Digestive System Diseases

Study Officials

• ObsEva SA

  Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 23, 2019
• Study Start: May 15, 2019
• Primary Completion: October 23, 2019
• Study Completion: November 1, 2019
• Last Updated: January 13, 2020

Record last verified: 2020-01

Locations

US (2)