Healthy Participants, Hepatic Impairment
Conditions
Keywords
Linzagolix, OBE2109, Hepatic Impairment, Hepatic Insufficiency, Liver Diseases, Clinical pharmacology study
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.
Interventions
DRUGLinzagolix
A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Sponsors
ObsEva SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 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 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 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 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 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 | predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose | Measurement of effect of hepatic impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment emergent Adverse Events | Day 1 to 14 days post-dose | 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 |
Countries
United States
Outcome results
None listed