ContraceptionPhase 1/2NCT01699022
Pharmacokinetic and Pharmacodynamic Study of Cyclofem
A Phase 1/2 study testing Injection Cyclofem in people with Contraception, run by Sun Pharmaceutical Industries Limited at 1 site in United States.
Trial 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)… Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- Injection Cyclofem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Dec 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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;
- Atypical squamous cells of undetermined significance (ASC-US) with positive reflex high-risk human papillomavirus (HPV) testing (Atypical squamous cells of undetermined significance [ASC-US]/human papillomavirus [HPV]+) or low-grade squamous intraepithelial lesion (LSIL) except when a colposcopy was performed (with or without biopsy) and found no evidence of high-grade disease (cervical intraepithelial neoplasia [CIN II] or worse) unless treatment is indicated per local standard of care;
- ASC-H, atypical glandular cells, or high grade squamous intraepithelial lesion (HSIL) unless treatment was received and follow-up at least 6 months after the treatment showed no evidence of disease; malignant cells;
- Current use of rifampin, griseofulvin, phenytoin, carbamazepine, barbiturates, or primidone;
- 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);
- 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;
- Active thyroid disease as measured by thyroid-stimulating hormone [TSH] levels ≤0.3 mU/L or ≥ 5 mU/L. Subjects with thyroid disease in good control with thyroid medication will be admitted.
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Research Center Norfolk, Virginia 601 Colley Avenue,
Norfolk, Virginia, 23507
About this study
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.
Read the 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 United States (US) market. Concept Foundation has licensed Sun Pharmaceutical Industries Ltd, Mumbai, India to manufacture and market Cyclofem® in India and other developing countries. United States Food and Drug Administration (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 Food and Drug Administration (FDA) for drug safety and efficacy. This initial pharmacokinetic (PK) study is the first step on the road to Food and Drug Administration (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 United States Food and Drug Administration (US FDA) would also allow the reintroduction of CICs to the United States (US) market.
- Conditions
- Contraception
- Being tested
- Injection Cyclofem
- Keywords
- Contraceptive, Injectable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection CyclofemDrug
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Injection Cyclofem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Medroxyprogesterone Acetate (MPA) Concentrations
Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85
Measured: "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).
Measured: "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
Measured: 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.
Measured: "Day 85"
Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2
Measured: "Day 85"
Estradiol (E2) Concentrations
Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85
Measured: "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.
Measured: Day 28
Tmax
Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection
Measured: "Day 85"
T1/2
Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)
Measured: "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.
Measured: Day 134
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2012 (estimated)
- Study startJun 2010
- Primary completionJul 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by Sun Pharmaceutical Industries LimitedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sun Pharmaceutical Industries Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David F Archer, MD, Principal investigator, Director, Conrad Clinical Research Center.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01699022
- Sponsor's protocol ID
- A09-109
- Status last verified
- Aug 2020
- First submitted
- 28 Sep 2012
- Last updated
- 2 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23265980
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic and Pharmacodynamic Study of Cyclofem
- ClinicalTrials.gov ID
- NCT01699022
- Acronym / sponsor ID
- A09-109
- Conditions
- Contraception
- Keywords
- Contraceptive, Injectable
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Sun Pharmaceutical Industries LimitedIndustry (pharma, biotech, devices)
- Study start
- Jun 2010
- Primary completion
- Jul 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 3 Oct 2012 (estimated)
- Results
- Posted 30 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 United States (US) market. Concept Foundation has licensed Sun Pharmaceutical Industries Ltd, Mumbai, India to manufacture and market Cyclofem® in India and other developing countries. United States Food and Drug Administration (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 Food and Drug Administration (FDA) for drug safety and efficacy. This initial pharmacokinetic (PK) study is the first step on the road to Food and Drug Administration (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 United States Food and Drug Administration (US FDA) would also allow the reintroduction of CICs to the United States (US) market.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Injection Cyclofem | Experimental | Drug: Injection CyclofemInjection 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (21 listed)
- Contraindications to the use of Cyclofem® include:
- Known hypersensitivity to any component of Cyclofem®
- Have an abnormal Pap smear in the past 12 months defined as:
- Current use of rifampin, griseofulvin, phenytoin, carbamazepine, barbiturates, or primidone;
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injection CyclofemAlso: CyclofemInjection 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 |
Primary outcome
Medroxyprogesterone Acetate (MPA) Concentrations
Time frame: "Day 1", "Day 29", "Day 57' and 'Day 85"
Assessment of mean trough levels of medroxyprogesterone acetate (MPA) on Day 1, Day 29, Day 57 and Day 85
Medroxyprogesterone Acetate (MPA) Pharmacokinetics
Time frame: "Day 85"
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).
Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax
Time frame: 85 days
The mean serum concentration-time profile for medroxyprogesterone acetate (MPA) after three consecutive monthly intramuscular administration of Cyclofem
Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax
Time frame: "Day 85"
Mean serum medroxyprogesterone acetate (MPA) concentrations peaked at 4.1 days (range 1 - 21 days) after the third monthly administration of Cyclofem.
Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2
Time frame: "Day 85"
Estradiol (E2) Concentrations
Time frame: "Day 1", "Day 29", "Day 57' and ''Day 85"
Mean serum estradiol (E2) concentrations on Day 1, Day 29, Day 57 and Day 85
Estradiol (E2) Pharmacokinetics.
Time frame: Day 28
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.
Tmax
Time frame: "Day 85"
Mean serum concentrations of estradiol (E2) peaked by 3.3 days (range 1 - 7 days) following the third monthly injection
T1/2
Time frame: "Day 85"
Mean no of days for medroxyprogesterone acetate (MPA) and estradiol (E2)
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration
Time frame: Day 134
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23265980Thurman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David F Archer, MD principal investigator
Director, Conrad Clinical Research Center.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Injection Cyclofem in people with Contraception, run by Sun Pharmaceutical Industries Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Medroxyprogesterone Acetate (MPA) Concentrations (time frame: "Day 1", "Day 29", "Day 57' and 'Day 85"). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01699022, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020.