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

ObsEva

Status and phase: Completed; Phase 1

Conditions: Renal Impairment; Healthy Participants

Treatments: Drug: Linzagolix

Study type: Interventional

Funder types: Industry

Identifiers

NCT03961932

18-OBE2109-010

Details and patient eligibility

About

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

Full 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.

Enrollment: 33 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 5 patient groups

Normal Renal Function

Experimental group

Description:

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

Treatment:

Drug: Linzagolix

Mild Renal Impairment

Experimental group

Description:

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

Treatment:

Drug: Linzagolix

Moderate Renal Impairment

Experimental group

Description:

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

Treatment:

Drug: Linzagolix

Severe Renal Impairment

Experimental group

Description:

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

Treatment:

Drug: Linzagolix

End-Stage Renal Disease

Experimental group

Description:

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

Treatment:

Drug: Linzagolix