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

Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Renal Function

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

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Healthy Participants
• Intervention / Treatment: Drug: Linzagolix

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Clinical Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Renal Function; Healthy participants with Normal Renal Function (estimated Glomerular Filtration Rate (eGFR) ≥ 90 mL/min/1.73m^2)	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: Mild Renal Impairment; Presence of Mild Renal Impairment (eGFR 60-89 mL/min/1.73m^2)	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: Moderate Renal Impairment; Presence of Moderate Renal Impairment (eGFR 30-59 mL/min/1.73m^2)	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: Severe Renal Impairment; Presence of Severe Renal Impairment (eGFR ≤ 29 mL/min/1.73m^2), not on hemodialysis	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions
Experimental: End-Stage Renal Disease; Presence of End-Stage Renal Disease (ESRD) requiring hemodialysis	Drug: Linzagolix; A single dose of 200 mg linzagolix (2 tablets of 100 mg) will be administered orally under fasting conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017	Measurement of effect of renal 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	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Plasma PK parameter Tmax of linzagolix and of KP017	Measurement of effect of renal impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Plasma PK parameter AUC0-t of linzagolix and of KP017	Measurement of effect of renal 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)	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose
Plasma PK parameter T1/2 of linzagolix and of KP017	Measurement of effect of renal impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)	predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent Adverse Events	Assessment of safety and tolerability of a single dose linzagolix in renal impaired subjects compared with healthy control subjects by assessing the number, frequency and severity of treatment emergent Adverse Events	Day 1 to 14 days post-dose

Collaborators and Investigators

• Sponsor: ObsEva SA
• Investigators: Study Director: ObsEva SA, Geneva

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2019
• Primary Completion (Actual): January 22, 2020
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 22, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Renal Insufficiency; Kidney Diseases; Renal impairment; Clinical pharmacology study; Linzagolix; OBE2109
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 18-OBE2109-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No