Pharmacokinetic and Pharmacodynamic Study of Cyclofem

NCT01699022 | Completed Phase 1 Results

• 1 other identifier: A09-109
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Cyclofem® is a monthly injectable contraceptive containing 25 mg of medroxyprogesterone acetate (MPA) and 5 mg of estradiol cypionate (E2C), a long-acting ester of estradiol. The current study will assess the steady-state pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate (MPA) and estradiol (E2) after administration of Cyclofem® and will provide critical information to determine similar bioavailability of Cyclofem to Lunelle in women residing in the United States of America.

Conditions

Contraception

Keywords

Contraceptive; Injectable

Outcome Measures

Primary Outcomes (10)

• Medroxyprogesterone Acetate (MPA) Concentrations

  Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85

  "Day 1", "Day 29", "Day 57' and 'Day 85"

• Medroxyprogesterone Acetate (MPA) Pharmacokinetics

  The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem (AUC). Peripheral blood sample for MPA was to be drawn three times a week for PK assessment during the third treatment month (Days 58, 60, 62, 64, 67, 69, 71, 75, 78, and 85) and for Day 85 (28 days post 3rd dose).

  "Day 85"

• Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax

  The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem

  85 days

• Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax

  Mean serum medroxyprogesterone acetate (MPA) concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.

  "Day 85"

• Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2

  "Day 85"

• Estradiol (E2) Concentrations

  Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85

  "Day 1", "Day 29", "Day 57' and ''Day 85"

• Estradiol (E2) Pharmacokinetics.

  AUC 0-28, AUC(0-inf). Peripheral blood sample for E2 was to be drawn three times a week for PK assessment during the third treatment month.

  Day 28

• Tmax

  Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection

  "Day 85"

• T1/2

  Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)

  "Day 85"

• Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration

  Return of ovulation measured by changes in serum progesterone concentration by analysis on Day 18, Day 21 (Control cycle), Day 103, Day 106, Day 131 and Day 134 indicating the number of subjects who achieved ovulation. Outcome measure description indicates what was measure.

  Day 134

Study Arms (1)

Injection Cyclofem

EXPERIMENTAL

Injection of Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials. Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.

Drug: Injection Cyclofem

Interventions

Injection Cyclofem DRUG

Injection Cyclofem contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate as a microcrystalline suspension in 0.5ml aqueous solution and is supplied in vials. Women were administered three consecutive monthly injections of Cyclofem for prevention of ovulation, and were followed until the 92nd day from the last (third) injection.

Also known as: Cyclofem

Injection Cyclofem

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between 18 and 45 years of age, inclusive;
• In good health, as evidenced by history and procedures at screening/enrollment visit
• Without any clinically significant systemic disease;
• Not at risk for pregnancy, having undergone surgical sterilization
• Have had regular menstrual cycles (every 21-35 days) for the past two cycles;
• Planning to reside in the area for at least 7 months after enrolling in the study; and
• Willing and able to comply with study procedures
• Have a body mass index (BMI) between 18 and 30 inclusive.

You may not qualify if:

• Contraindications to the use of Cyclofem® include:
• Smoking any number of cigarettes per day in a woman \> 35 years old (or in a woman 34 years-old who will turn 35 years-old during the study),
• Symptoms of chest pain or shortness of breath,
• Screening visit blood pressure \>140/90, (subjects on hypertensive medications, in good blood pressure control will be admitted).
• Past or current thrombophlebitis or thromboembolic disorders,
• Past or current cerebral vascular or coronary artery disease
• History of stroke, myocardial infarction or ischemic heart disease or complicated valvular heart disease
• Diabetes
• Past or current carcinoma of the endometrium cervix or vagina; breast or other known or suspected estrogen-depended neoplasia,
• Headaches with focal neurological symptoms,
• Unexplained abnormal vaginal bleeding,
• Liver dysfunction or disease, such as a history of hepatic adenoma or carcinoma; history of cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use including severe pruritus of pregnancy, severe cirrhosis, or active hepatitis (defined as aspartate aminotransferase \[AST or SGOT ≥ 120 IU/L\] or alanine aminotransferase \[ALT or SGPT ≥ 135 IU/L\]) or clinically significant laboratory abnormalities as judged by the physician evaluating the individual subject).
• Known hypersensitivity to any component of Cyclofem®
• Have an abnormal Pap smear in the past 12 months defined as:
• Atypical squamous cells of undetermined significance (ASC-US) without a normal repeat Pap smear at least 6 months later;

Sponsors & Collaborators

• Sun Pharmaceutical Industries Limited: lead

Study Sites (1)

Clinical Research Center Norfolk, Virginia 601 Colley Avenue,

Norfolk, Virginia, 23507, United States

Location

Related Publications (1)

• Thurman A, Kimble T, Hall P, Schwartz JL, Archer DF. Medroxyprogesterone acetate and estradiol cypionate injectable suspension (Cyclofem) monthly contraceptive injection: steady-state pharmacokinetics. Contraception. 2013 Jun;87(6):738-43. doi: 10.1016/j.contraception.2012.11.010. Epub 2012 Dec 22.

  PMID: 23265980 DERIVED

MeSH Terms

Interventions

CycloProvera

Results Point of Contact

• Title: Dr. Shravanti Bhowmik
• Organization: SPARC

shravanti.bhowmik@sparcmail.com

02266455645

Study Officials

• David F Archer, MD

  Director, Conrad Clinical Research Center.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2012
• First Posted: October 3, 2012
• Study Start: June 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: December 1, 2011
• Last Updated: September 2, 2020
• Results First Posted: December 30, 2013

Record last verified: 2020-08

Locations

US (1)