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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03961932
• Other study ID #: 18-OBE2109-010
• Status: Completed
• Phase: Phase 1
• Start date: May 15, 2019
• Est. completion date: January 31, 2020

Study information

• Verified date: March 2020
• Source: ObsEva SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 31, 2020
• Est. primary completion date: January 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy Participants
• Renal Impairment
• Renal Insufficiency

Intervention

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

Locations

Country	Name	City	State
United States	Clinical Site	Orlando	Florida
United States	Clinical Site	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
ObsEva SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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