Clinical trial NCT03961932: Safety and Pharmacokinetics of Linzagolix in Female Subjects With Normal and Impaired Renal Function
Official title: Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Healthy Participants
Keywords: Linzagolix
OBE2109
Renal impairment
Renal Insufficiency
Kidney Diseases
Clinical pharmacology study
Lead sponsor: ObsEva SA
Sponsor class: INDUSTRY
First posted: 2019-05-23
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
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 renal function compared to matched control subjects with normal renal function

Detailed description: This is a Phase 1, non-randomized, open label, single-dose study to evaluate the effect of varying degrees of impaired renal function (i.e., mild, moderate, severe Renal Impairment (RI), and End-Stage Renal Disease (ESRD) on hemodialysis) on the PK, safety, and tolerability of linzagolix and its major metabolite, KP017.

Up to 40 adult female participants will be enrolled.

Eligibility criteria: Key Inclusion Criteria:

Renal Impaired Subjects

1. Adult female, ≥ 18 years of age at screening
2. Has a BMI ≥ 18.0 and ≤ 42.0 kg/m\^2 and weight ≥ 40 kg, at screening
3. Aside from RI, 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

   Subjects with mild, moderate, or severe RI:
4. Has estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) equation at screening as follows:

   * Severe RI only: ≤ 29 mL/min/1.73m\^2 not on hemodialysis
   * Moderate RI only: 30 - 59 mL/min/1.73m\^2
   * Mild RI only: 60 - 89 mL/min/1.73m\^2
5. Has a stable renal function with no clinically significant change in renal status at least 1 month prior to study drug administration and is not currently or has not been previously on hemodialysis for at least 1 year

   Subjects with ESRD:
6. Subject is maintained on a stable hemodialysis regimen at least 3 times a week for at least 3 months prior to dosing

Healthy Subjects

1. Health adult female will be matched to subjects with RI
2. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee
3. Baseline eGFR ≥ 90 mL/min/1.73m\^2 at screening, based on the MDRD equation. Actual creatinine clearance, as determined by a 24-hour urine collection, may be used in place of or in conjunction with the MDRD equation at the PI's discretion

Key Exclusion Criteria:

Renal Impaired Subjects

1. Had any major surgery within 4 weeks prior to dosing
2. Presence of functioning renal transplant
3. Has a surgical (e.g., hepatectomy, nephrectomy, digestive organ resection) or medical condition other than RI 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 judge 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: Orlando
country: United States
facility: Clinical Site
state: Florida
city: Saint Paul
country: United States
facility: Clinical Site
state: Minnesota
Study officials:
affiliation: Geneva
name: ObsEva SA
role: STUDY_DIRECTOR
References: