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

Primary Purpose

Renal Impairment, Healthy Participants

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Linzagolix

About this trial

This is an interventional basic science trial for Renal Impairment focused on measuring Linzagolix, OBE2109, Renal impairment, Renal Insufficiency, Kidney Diseases, Clinical pharmacology study

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Key Inclusion Criteria:

Renal Impaired Subjects

Adult female, ≥ 18 years of age at screening
Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening
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:
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
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:
Subject is maintained on a stable hemodialysis regimen at least 3 times a week for at least 3 months prior to dosing

Healthy Subjects

Health adult female will be matched to subjects with RI
Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee
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

Had any major surgery within 4 weeks prior to dosing
Presence of functioning renal transplant
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

Has any clinically significant illness, as judge by the PI or designee, within 4 weeks prior to dosing
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

Sites / Locations

Clinical Site
Clinical Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Normal Renal Function

Mild Renal Impairment

Moderate Renal Impairment

Severe Renal Impairment

End-Stage Renal Disease

Arm Description

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

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

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

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

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

Outcomes

Primary Outcome Measures

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

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)

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)

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)

Secondary Outcome Measures

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

Full Information

NCT ID

NCT03961932

First Posted

May 20, 2019

Last Updated

March 4, 2020

Sponsor

ObsEva SA

1. Study Identification

Unique Protocol Identification Number

NCT03961932

Brief Title

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

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

May 15, 2019 (Actual)

Primary Completion Date

January 22, 2020 (Actual)

Study Completion Date

January 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ObsEva SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Impairment, Healthy Participants

Keywords

Linzagolix, OBE2109, Renal impairment, Renal Insufficiency, Kidney Diseases, Clinical pharmacology study

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

33 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal Renal Function

Arm Type

Experimental

Arm Description

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

Arm Title

Mild Renal Impairment

Arm Type

Experimental

Arm Description

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

Arm Title

Moderate Renal Impairment

Arm Type

Experimental

Arm Description

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

Arm Title

Severe Renal Impairment

Arm Type

Experimental

Arm Description

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

Arm Title

End-Stage Renal Disease

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Linzagolix

Intervention Description

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

Primary Outcome Measure Information:

Title

Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017

Description

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Title

Plasma PK parameter Tmax of linzagolix and of KP017

Description

Measurement of effect of renal impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Title

Plasma PK parameter AUC0-t of linzagolix and of KP017

Description

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Title

Plasma PK parameter T1/2 of linzagolix and of KP017

Description

Measurement of effect of renal impairment on PK of linzagolix and its metabolite KP017 by assessment of the T1/2 (Terminal half life)

Time Frame

predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose

Secondary Outcome Measure Information:

Title

Treatment emergent Adverse Events

Description

Time Frame

Day 1 to 14 days post-dose

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Renal Impaired Subjects Adult female, ≥ 18 years of age at screening Has a BMI ≥ 18.0 and ≤ 42.0 kg/m^2 and weight ≥ 40 kg, at screening 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: 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 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: Subject is maintained on a stable hemodialysis regimen at least 3 times a week for at least 3 months prior to dosing Healthy Subjects Health adult female will be matched to subjects with RI Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee 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 Had any major surgery within 4 weeks prior to dosing Presence of functioning renal transplant 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 Has any clinically significant illness, as judge by the PI or designee, within 4 weeks prior to dosing 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

ObsEva SA

Organizational Affiliation

Geneva

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

Facility Name

Clinical Site

City

Saint Paul

State/Province

Minnesota

ZIP/Postal Code

55114

Country

United States

12. IPD Sharing Statement

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

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