Study of Ulipristal Acetate in Female Patients With Moderately or Severely Impaired Renal Function, Compared With Matched Healthy Female Subjects

A Single-Dose, Open-Label, Pharmacokinetic Study Of Ulipristal Acetate In Healthy Subjects With Normal Renal Function And Patients With Moderately Or Severly Impaired Renal Function

This study is designed to observe the effect of renal function on the pharmacokinetic, safety, and tolerability profiles of Ulipristal acetate following administration of a single oral dose of a 10 mg Ulipristal acetate tablet.

Study Overview

• Status: Completed
• Conditions: Renal Function
• Intervention / Treatment: Drug: Ulipristal acetate

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33104
      • Division of Clinical Pharmacology, University of Miami
    • Miami, Florida, United States, 33136
      • Clinical Pharmacology of Miami
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Clinical Research
  • Missouri
    • Springfield, Missouri, United States, 65802
      • QPS Bio-Kinetic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria for Patients with Renal Impairment:

• Have a negative result from a serum pregnancy test at screening and a negative result from a serum or urine pregnancy test on Day -1
• If premenopausal, have regular menstrual cycles (cycles of 24-35 days duration) over the past 6 months as reported by the patient
• If female of childbearing potential, agree to use an effective method of contraception (i.e., condom plus diaphragm with spermicide, condom with spermicide, or nonhormonal intrauterine device) and not become pregnant throughout the study. Subjects who are at least 2-years postmenopausal (with supporting documentation from an obstetrician/gynecologist) or who have had tubal ligation or hysterectomy will not be considered to be of childbearing potential
• Be nonsmoking (never smoked or have not smoked within the previous 6 months) or a light smoker (fewer than 10 cigarettes per day within the previous 3 months)
• For Patients with Renal Impairment, have medical history, physical examination, laboratory, and other test results consistent with their degree of renal impairment, as determined by the Investigator
• For Patients with Normal Renal Function, have a state of general good health based on medical history and routine physical examination and are matched to the age and weight of the renal dysfunction patients (mean group difference ±10 years for age and < 20% for weight)

Exclusion Criteria:

• Known hypersensitivity to Ulipristal Acetate (UPA) or other selective progesterone receptor modulators
• For Patients with Renal Impairment, clinically significant disease state, in the opinion of the examining physician, in any body system (other than renal function impairment)
• For Patients with Normal Renal Function, clinically significant disease state, in the opinion of the examining physician, in any body system
• Positive test results for anti-human immunodeficiency virus type 1, hepatitis B surface antigen, or anti-hepatitis C virus at screening
• Abnormal and clinically significant results on physical examination, medical history, serum chemistry, hematology, or urinalysis
• History of alcohol or other substance abuse within the previous 5 years
• Positive test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, or phencyclidine at screening or Day -1. Patients with Renal Impairment many be enrolled if the positive test result is due to prescription drug use and approved by the Principal Investigator and Sponsor Study Physician, on a case-by-case basis
• Participation in any other clinical investigation using an experimental drug requiring repeated blood or plasma draws within 30 days of IP administration
• Participation in a blood or plasma donation program within 60 or 30 days, respectively, of Investigational Product (IP) administration
• Previously participated in an investigational study of Ulipristal Acetate
• Breastfeeding

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Renal Function; Ulipristal acetate, 10 mg, oral administration	Drug: Ulipristal acetate
Experimental: Moderate Renal Impairment; Ulipristal acetate, 10 mg, oral administration	Drug: Ulipristal acetate
Experimental: Severe Renal Impairment; Ulipristal acetate, 10 mg, oral administration	Drug: Ulipristal acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve of ulipristal acetate from time 0 to time t (AUC 0-t)	Day 1 (0 hour) to Day 8 (168 hours)
Maximum plasma drug concentration (Cmax) of ulipristal acetate	Day 1 (0 hour) to Day 8 (168 hours)
Time of maximum plasma drug concentration (Tmax) of ulipristal acetate	Day 1 (0 hour) to Day 8 (168 hours)
Terminal elimination half-life (T½) of ulipristal acetate	Day 1 (0 hour) to Day 8 (168 hours)
Apparent total body clearance of ulipristal acetate from plasma after extravascular administration (CL/F) of ulipristal acetate	Day 1 (0 hour) to Day 8 (168 hours)
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of ulipristal acetate	Day 1 (0 hour) to Day 8 (168 hours)
Area under the plasma concentration versus time curve of ulipristal acetate from time 0 to infinity (AUC 0-∞)	Day 1 (0 hour) to Day 8 (168 hours)

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve of PGL4002 (ulipristal acetate active metabolite) from time 0 to time t (AUC 0-t)	Day 1 (0 hour) to Day 8 (168 hours)
Time of maximum plasma drug concentration (Tmax) of PGL4002 (ulipristal acetate active metabolite)	Day 1 (0 hour) to Day 8 (168 hours)
Terminal elimination half-life (T½) of PGL4002 (ulipristal acetate active metabolite)	Day 1 (0 hour) to Day 8 (168 hours)
Maximum plasma drug concentration (Cmax) of PGL4002 (ulipristal acetate active metabolite)	Day 1 (0 hour) to Day 8 (168 hours)
Cumulative amount of ulipristal acetate excreted into urine from time zero to time t (Ae0-t)	Day 1 (0 hour) to Day 8 (168 hours)
Renal clearance of ulipristal acetate from plasma (CLR)	Day 1 (0 hour) to Day 8 (168 hours)
Percent of dose excreted as unchanged ulipristal acetate in urine (%Dose)	Day 1 (0 hour) to Day 8 (168 hours)
Cumulative amount of PGL4002 excreted into urine from time zero to time t (Ae0-t)	Day 1 (0 hour) to Day 8 (168 hours)
Renal clearance of PGL4002 from plasma (CLR)	Day 1 (0 hour) to Day 8 (168 hours)
Area under the plasma concentration versus time curve of PGL4002 (ulipristal acetate active metabolite) from time 0 to infinity (AUC 0-∞)	Day 1 (0 hour) to Day 8 (168 hours)

Collaborators and Investigators

• Sponsor: Allergan
• Investigators: Study Director: Laishun Chen, Forest Laboratories Inc, an affiliate of Allergan plc

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 9, 2016
• Study Completion (Actual): December 9, 2016

Study Registration Dates

• First Submitted: December 16, 2015
• First Submitted That Met QC Criteria: December 17, 2015
• First Posted (Estimate): December 18, 2015

Study Record Updates

• Last Update Posted (Actual): February 8, 2018
• Last Update Submitted That Met QC Criteria: February 6, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Ulipristal acetate
• Other Study ID Numbers: UPA-PK-02