Pharmacokinetic and Pharmacodynamic Study of Cyclofem

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sun Pharmaceutical Industries Limited
ClinicalTrials.gov Identifier:
NCT01699022
First received: September 28, 2012
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

Cyclofem® is a monthly injectable contraceptive containing 25 mg of 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 MPA and E2 after administration of Cyclofem® and will provide critical information to determine similar bioavailability of Cyclofem to Lunelle in women residing in the USA.


Condition Intervention Phase
Contraception
Drug: Injection Cyclofem
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pharmacokinetic and Pharmacodynamic Study of Cyclofem

Resource links provided by NLM:


Further study details as provided by Sun Pharmaceutical Industries Limited:

Primary Outcome Measures:
  • MPA Concentrations [ Time Frame: "Day 1", "Day 29", "Day 57' and 'Day 85" ] [ Designated as safety issue: Yes ]
    Assessment of mean trough levels of MPA on Day 1, Day 29, Day 57 and Day 85

  • MPA Pharmacokinetics [ Time Frame: "Day 85" ] [ Designated as safety issue: No ]
    The mean serum concentration-time profile for MPA after three consecutive monthly intramuscular administration of Cyclofem (AUC)

  • MPA Pharmacokinetics Cmax [ Time Frame: 85 days ] [ Designated as safety issue: No ]
    The mean serum concentration-time profile for MPA after three consecutive monthly intramuscular administration of Cyclofem

  • MPA Pharmacokinetics Tmax [ Time Frame: "Day 85" ] [ Designated as safety issue: No ]
    Mean serum MPA concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.

  • MPA Pharmacokinetics T1/2 [ Time Frame: "Day 85" ] [ Designated as safety issue: No ]
  • E2 Concentrations [ Time Frame: "Day 1", "Day 29", "Day 57' and ''Day 85" ] [ Designated as safety issue: No ]
    Mean serum E2 concentrations on Day 1, Day 29, Day 57 and Day 85

  • E2 Pharmacokinetics [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
    AUC 0-28, AUC(0-inf)

  • Tmax [ Time Frame: "Day 85" ] [ Designated as safety issue: No ]
    Mean serum concentrations of E2 peaked by 3.3 days (range 1 - 7 days) following the third monthly injection

  • T1/2 [ Time Frame: "Day 85" ] [ Designated as safety issue: No ]
    Mean no of days for MPA and E2

  • Serum Progesterone Concentration [ Time Frame: Day 134 ] [ Designated as safety issue: No ]

    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



Enrollment: 17
Study Start Date: June 2010
Study Completion Date: December 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Injection Cyclofem

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

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.

Other Name: Cyclofem

Detailed Description:

Concept Foundation, an international nonprofit organization based in Bangkok, Thailand, was given the commercial rights to Cyclofem® by the World Health Organization (WHO) for use internationally. The brand names that the Concept Foundation has registered internationally include Cyclofem®, and Novafem® (Pharmacia Pharmaceuticals, Peapack NJ, formerly (Pharmacia and Upjohn of Kalamazoo, Michigan). The company launched its product under license from Concept Foundation with their own brand name, Lunelle™ in the US market. Lunelle™ was approved by the Food and Drug Administration (FDA) in October, 2000 following which approximately 350,000 women had used the product. However, following the acquisition of Pharmacia and Upjohn by Pfizer and due to several production problems, Pfizer withdrew Lunelle™ from the US market. Concept Foundation has licensed Sun Pharmaceutical Industries Ltd, Mumbai, India to manufacture and market Cyclofem® in India and other developing countries. US FDA approval of Cyclofem® is pivotal to the ultimate acceptance of such products in many countries because of the rigorous standards applied by the FDA for drug safety and efficacy. This initial PK study is the first step on the road to FDA approval with the ultimate goal to expand the access and range of methods available to women in the public sector. Approval of Cyclofem® by the US FDA would also allow the reintroduction of CICs to the US market.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Contraindications to the use of Cyclofem® include:

    1. 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),
    2. Symptoms of chest pain or shortness of breath,
    3. Screening visit blood pressure >140/90, (subjects on hypertensive medications, in good blood pressure control will be admitted).
    4. Past or current thrombophlebitis or thromboembolic disorders,
    5. Past or current cerebral vascular or coronary artery disease
    6. History of stroke, myocardial infarction or ischemic heart disease or complicated valvular heart disease
    7. Diabetes
    8. Past or current carcinoma of the endometrium cervix or vagina; breast or other known or suspected estrogen-depended neoplasia,
    9. Headaches with focal neurological symptoms,
    10. Unexplained abnormal vaginal bleeding,
    11. 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).
  2. Known hypersensitivity to any component of Cyclofem®
  3. Have an abnormal Pap smear in the past 12 months defined as:

    1. ASC-US without a normal repeat Pap smear at least 6 months later;
    2. ASC-US with positive reflex high-risk HPV testing (ASC-US/HPV+) or LSIL except when a colposcopy was performed (with or without biopsy) and found no evidence of high-grade disease (CIN II or worse) unless treatment is indicated per local standard of care;
    3. ASC-H, atypical glandular cells, or HSIL unless treatment was received and follow-up at least 6 months after the treatment showed no evidence of disease; malignant cells;
  4. Current use of rifampin, griseofulvin, phenytoin, carbamazepine, barbiturates, or primidone;
  5. Other conditions that, in the opinion of the investigator, would constitute contraindications to participation in the study or would compromise ability to comply with the study protocol, such as any major chronic illness including cancer, serious autoimmune disease or a major psychiatric disorder (e.g. schizophrenia);
  6. Current participation in any other drug or device study, or any study which, in the opinion of the investigator, would jeopardize interpretation of results of this study;
  7. Active thyroid disease (as measured by TSH levels ≤0.3 mU/L or ≥ 5 mU/L. Subjects with thyroid disease in good control with thyroid medication will be admitted.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01699022

Locations
United States, Virginia
Clinical Research Center Norfolk, Virginia 601 Colley Avenue,
Norfolk,, Virginia, United States, 23507
Sponsors and Collaborators
Sun Pharmaceutical Industries Limited
Investigators
Principal Investigator: David F Archer, MD Director, Conrad Clinical Research Center.
  More Information

No publications provided by Sun Pharmaceutical Industries Limited

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sun Pharmaceutical Industries Limited
ClinicalTrials.gov Identifier: NCT01699022     History of Changes
Other Study ID Numbers: A09-109
Study First Received: September 28, 2012
Results First Received: December 12, 2012
Last Updated: December 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sun Pharmaceutical Industries Limited:
Contraceptive
Injectable

Additional relevant MeSH terms:
Estradiol 17 beta-cypionate
Medroxyprogesterone
Medroxyprogesterone Acetate
CycloProvera
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Contraceptives, Oral, Combined

ClinicalTrials.gov processed this record on August 18, 2014