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

NCT ID: NCT03961932

Last Updated: 2020-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-15
• Study Completion Date: 2020-01-31

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.

Conditions

Renal Impairment; Healthy Participants

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Normal Renal Function

Healthy participants with Normal Renal Function (estimated Glomerular Filtration Rate (eGFR) ≥ 90 mL/min/1.73m\^2)

Group Type: EXPERIMENTAL

Linzagolix

Intervention Type: DRUG

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

Mild Renal Impairment

Presence of Mild Renal Impairment (eGFR 60-89 mL/min/1.73m\^2)

Group Type: EXPERIMENTAL

Linzagolix

Intervention Type: DRUG

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

Moderate Renal Impairment

Presence of Moderate Renal Impairment (eGFR 30-59 mL/min/1.73m\^2)

Group Type: EXPERIMENTAL

Linzagolix

Intervention Type: DRUG

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

Severe Renal Impairment

Presence of Severe Renal Impairment (eGFR ≤ 29 mL/min/1.73m\^2), not on hemodialysis

Group Type: EXPERIMENTAL

Linzagolix

Intervention Type: DRUG

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

End-Stage Renal Disease

Presence of End-Stage Renal Disease (ESRD) requiring hemodialysis

Group Type: EXPERIMENTAL

Linzagolix

Intervention Type: DRUG

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

Interventions

Linzagolix

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

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

ObsEva SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ObsEva SA

Role: STUDY_DIRECTOR

Geneva

Locations

Clinical Site

Orlando, Florida, United States

Clinical Site

Saint Paul, Minnesota, United States

Countries

United States

Other Identifiers

18-OBE2109-010

Identifier Type: -

Identifier Source: org_study_id