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

NCT03961932 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-OBE2109-010
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

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

Conditions

Renal Impairment; Healthy Participants

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Treatment emergent Adverse Events

  Day 1 to 14 days post-dose

Study Arms (5)

Normal Renal Function

EXPERIMENTAL

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

Drug: Linzagolix

Mild Renal Impairment

EXPERIMENTAL

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

Drug: Linzagolix

Moderate Renal Impairment

EXPERIMENTAL

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

Drug: Linzagolix

Severe Renal Impairment

EXPERIMENTAL

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

Drug: Linzagolix

End-Stage Renal Disease

EXPERIMENTAL

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

Drug: Linzagolix

Interventions

Linzagolix DRUG

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

End-Stage Renal Disease; Mild Renal Impairment; Moderate Renal Impairment; Normal Renal Function; Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ObsEva SA: lead

Study Sites (2)

Clinical Site

Orlando, Florida, 32809, United States

Location

Clinical Site

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases

Interventions

linzagolix

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• ObsEva SA

  Geneva

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 23, 2019
• Study Start: May 15, 2019
• Primary Completion: January 22, 2020
• Study Completion: January 31, 2020
• Last Updated: March 5, 2020

Record last verified: 2020-03

Locations

US (2)