Characterization of the Pharmacokinetics of a Vaginal Ring With 2.0 g Progesterone in Post-menopausal Women

NCT03737656 | Completed Phase 1

• 3 other identifiers: PRG-02-GRU/PK-PVR-0116-CI-19 039 043HP8013-01
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single site, open-label, randomized, single-dose, Phase 1 study in post-menopausal women.

Conditions

Pharmacokinetics

Keywords

Progesterone; Vaginal ring

Outcome Measures

Primary Outcomes (3)

• Progesterone pharmacokinetic parameters (AUC0-t)

  In Groups A, B, and C, 3 blood samples will be obtained before the device is placed and 24 samples after placement of the device up to Day 91. Additional samples (6 samples in Group B and 8 samples in Group C) will be taken while the ring is removed/after the ring is re-inserted on Day 28. Eight blood samples will be taken from all participants (from Groups A, B, and C) within 24 hours after the ring is removed on Day 91. Plasma concentrations of progesterone will be determined using validated analytical methods. The baseline-corrected and uncorrected area under the plasma concentration-time curve from 0 to time t (AUC0-t) will be calculated.

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

• Progesterone pharmacokinetic parameters (AUC0-inf)

  In Groups A, B, and C, 3 blood samples will be obtained before the device is placed and 24 samples after placement of the device up to Day 91. Additional samples (6 samples in Group B and 8 samples in Group C) will be taken while the ring is removed/after the ring is re-inserted on Day 28. Eight blood samples will be taken from all participants (from Groups A, B, and C) within 24 hours after the ring is removed on Day 91. Plasma concentrations of progesterone will be determined using validated analytical methods. The baseline-corrected and uncorrected area under the plasma concentration-time curve from 0 to infinity (AUC0-inf) will be calculated.

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

• Progesterone pharmacokinetic parameters (Cmax)

  In Groups A, B, and C, 3 blood samples will be obtained before the device is placed and 24 samples after placement of the device up to Day 91. Additional samples (6 samples in Group B and 8 samples in Group C) will be taken while the ring is removed/after the ring is re-inserted on Day 28. Eight blood samples will be taken from all participants (from Groups A, B, and C) within 24 hours after the ring is removed on Day 91. Plasma concentrations of progesterone will be determined using validated analytical methods. The baseline-corrected and uncorrected maximum plasma concentration (Cmax) will be calculated.

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

Secondary Outcomes (4)

• Progesterone pharmacokinetic parameters (Tmax)

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

• Progesterone pharmacokinetic parameters (AUC%extr)

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

• Progesterone pharmacokinetic parameters (t1/2)

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

• Progesterone pharmacokinetic parameters (MRT)

  Insertion of ring (Day 1) to removal of ring (Day 91) plus 24 hours

Study Arms (3)

Progesterone Vaginal Ring (Group A)

EXPERIMENTAL

Insertion of the vaginal ring on Day 1 and continuous use until 91 days of treatment are completed. In this group, 28 participants will be included.

Drug: Progesterone vaginal ring

Progesterone Vaginal Ring (Group B)

EXPERIMENTAL

Insertion of the vaginal ring on Day 1, removal for 2 hours on study Day 28, re-insertion on Day 28, and continuous use for 63 days until 91 days of treatment are completed. In this group, 6 participants will be included.

Drug: Progesterone vaginal ring

Progesterone Vaginal Ring (Group C)

EXPERIMENTAL

Insertion of the vaginal ring on Day 1, removal for 4 hours on study Day 28, re-insertion on Day 28, and continuous use for 63 days until 91 days of treatment are completed. In this group, 6 participants will be included.

Drug: Progesterone vaginal ring

Interventions

Progesterone vaginal ring DRUG

Vaginal ring with 2.0 g progesterone (sustained-release over 90-days)

Also known as: Progering (Trade Mark)

Progesterone Vaginal Ring (Group A); Progesterone Vaginal Ring (Group B); Progesterone Vaginal Ring (Group C)

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Only post-menopausal women aged between 40 years and 65 years who are currently not in hormone replacement therapy and who meet any of the following criteria:
• months of spontaneous and continuous amenorrhea.
• months of spontaneous amenorrhea with follicle-stimulating hormone levels above 40 international units/liter and less than 20 picograms per milliliter estradiol.
• Bilateral oophorectomy without hysterectomy.
• B. The body mass index must be between 18.5 and 29.99 kilograms per square meter according to the Quetelet index.
• C. Participants must be healthy determined by the results of a complete clinical history recorded by the clinical investigational site and the results of the laboratory examinations done by a certified clinical laboratory.
• D. Participants with pre-existing illnesses must be controlled with stable doses of medication for a period of at least 3 months.
• E. The allowed limits of variation within normal in the screening visit will be: systolic blood pressure (sitting) less or equal to 130 mmHg, diastolic blood pressure less or equal to 80 mmHg, pulse rate between 50 and 100 beats per minute for 1 minute and respiratory rate between 14 and 20 breaths per minute.
• Complete blood count: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte distribution width, platelets, neutrophils, lymphocytes, monocytes, eosinophils.
• Blood chemistry 27 elements: glucose, urea, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, uric acid, cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein cholesterol, non-HDL cholesterol, atherogenic index, total protein, albumin, globulins, albumin/globulin ratio, total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, total alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, iron, calcium, sodium, potassium, and chloride.
• Urinalysis: Physical examination (color, appearance, density); chemical examination (pH, leukocytes, nitrite, protein, glucose, ketones, bilirubin, urobilinogen, hemoglobin); microscopic examination (leukocytes, erythrocytes, dysmorphic erythrocytes, casts, crystals, squamous epithelial cells, tubular renal cells, mucus, bacteria and yeasts).
• Hepatitis B screening (antibody to hepatitis B core antigen \[Anti-HBc\], antibody to hepatitis B surface antigen \[HBs-Ab\], antibody to hepatitis B surface antigen \[Anti-HBs\]) and hepatitis C antibodies.
• HIV test: Antibodies to the human immunodeficiency virus (Anti-HIV 1 and 2).
• Venereal disease research laboratory test (VDRL).
• Drugs of abuse test at the screening visit and approximately 12 hours before insertion of the vaginal ring on Day 1.

You may not qualify if:

• B. Participants with a history of the following diseases: cardiovascular (myocardial infarction, not-controlled hypertension, thromboembolic, arterial or venous diseases), renal (kidney failure), hepatic (hepatitis, cholestatic jaundice, hepatic tumors, Dubin-Johnson syndrome, Rotor syndrome), muscular, metabolic, gastrointestinal including constipation, neurologic (cerebrovascular disease), endocrinological (not-controlled diabetes), hematopoietic or any type of anemia, history of toxic shock due to Staphylococcus, asthma, mental disorder (depression) or other organic abnormalities that are not appropriately controlled and that require a pharmacological treatment that could result in a drug interaction with the study medication. Women who have had muscular trauma within 21 days previous to the study will also be excluded.
• C. Participants with uterine bleeding.
• D. Participants with endometrial thickness equal to or greater than 7 millimeters as determined in the transvaginal ultrasound.
• E. Participants with history of dyspepsia, gastritis, esophagitis, duodenal or gastric ulcer.
• F. Hypersensitivity or allergy to the study medication.
• G. Participants who have been exposed to medications known to be enzyme inducers or inhibitors or women who have taken potentially toxic medications within 72 hours previous to the start of each study period.
• H. Participants undergoing hormone replacement therapy or taking thyroid hormones in the last 3 months.
• I. Participants who have been hospitalized for any reason within 6 months prior to study start.
• J. Participants who have taken investigational medicinal products from other investigations within 180 days (i.e., 6 months) prior to study start.
• K. Participants who have smoked tobacco within 12 hours prior to study days 1, 28, and 91.
• L. Participants who have donated or lost more than 450 milliliters of blood within 60 days prior to study start.
• M. Participants with a history of drug abuse or alcoholism.
• N. Participants requiring a special diet for any reason e.g., vegetarian.
• O. Participants unable to understand the nature, objectives, and possible consequences of the study.
• P. Evidence of the participant's uncooperativeness during the conduct of the study.

Sponsors & Collaborators

• Grünenthal GmbH: lead
• Grünenthal, S.A.: collaborator

Study Sites (1)

Investigacíon Farmacológica y Biofarmacéutica (IFaB), S.A.P.I. de C.V.

Mexico City, C.P. 14610, Mexico

Location

Study Officials

• Grünenthal Study Director

  Grünenthal GmbH

  STUDY DIRECTOR

Study Design

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

Model Details: Single site, open-label, randomized, single-dose, with three groups.

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 9, 2018
• Study Start: November 1, 2018
• Primary Completion: May 3, 2019
• Study Completion: May 9, 2019
• Last Updated: June 5, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

ME (1)