Clinical trial NCT03962049: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Healthy Participants
Keywords: Linzagolix
OBE2109
Hepatic Impairment
Hepatic Insufficiency
Liver Diseases
Clinical pharmacology study
Lead sponsor: ObsEva SA
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017
timeFrame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: Plasma PK parameter Tmax of linzagolix and of KP017
timeFrame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: Plasma PK parameter AUC0-t of linzagolix and of KP017
timeFrame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
measure: Plasma PK parameter T1/2 of linzagolix and of KP017
timeFrame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Secondary outcomes:
measure: Treatment emergent Adverse Events
timeFrame: Day 1 to 14 days post-dose
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Clinical Site
state: Florida
city: Orlando
country: United States
facility: Clinical Site
state: Florida
Study officials:
affiliation: Geneva
name: ObsEva SA
role: STUDY_DIRECTOR
References: