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

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ClinicalTrials.gov Identifier: NCT03961932
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : May 27, 2019
Sponsor:
Information provided by (Responsible Party):
ObsEva SA

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

Condition or disease Intervention/treatment Phase
Renal Impairment Healthy Participants Drug: Linzagolix Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Evaluation of the Safety and Pharmacokinetics of a Single Dose of Linzagolix in Female Subjects With Normal and Impaired Renal Function
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Tests

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




Primary Outcome Measures :
  1. Plasma pharmacokinetic (PK) parameter Cmax of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    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

  2. Plasma PK parameter Tmax of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    Measurement of effect of renal impairment on PK of linzagolix and its metabolite KP017 by assessment of the Time to reach Cmax (Tmax)

  3. Plasma PK parameter AUC0-t of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    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)

  4. Plasma PK parameter T1/2 of linzagolix and of KP017 [ Time Frame: predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose ]
    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 :
  1. Treatment emergent Adverse Events [ Time Frame: Day 1 to 14 days post-dose ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03961932


Contacts
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Contact: Clinical Trial Director +41 (0) 22 552 3840 clinicaltrials@obseva.ch

Locations
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United States, Florida
Clinical Site Recruiting
Orlando, Florida, United States, 32809
United States, Minnesota
Clinical Site Recruiting
Saint Paul, Minnesota, United States, 55114
Sponsors and Collaborators
ObsEva SA
Investigators
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Study Director: ObsEva SA Geneva

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Responsible Party: ObsEva SA
ClinicalTrials.gov Identifier: NCT03961932     History of Changes
Other Study ID Numbers: 18-OBE2109-010
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: May 27, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ObsEva SA:
Linzagolix
OBE2109
Renal impairment
Renal Insufficiency
Kidney Diseases
Clinical pharmacology study

Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases