Trial Outcomes & Findings for Pharmacokinetic and Pharmacodynamic Study of Cyclofem (NCT NCT01699022)

NCT ID: NCT01699022

Last Updated: 2020-09-02

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: "Day 1", "Day 29", "Day 57' and 'Day 85"
• Results posted on: 2020-09-02

Participant Flow

The study was conducted at the CONRAD Clinical Research Center (CRC) located in the Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School (EVMS) in Norfolk, vasectomy (VA) in subjects with previous surgical sterilization and therefore were not at risk for pregnancy

A total of 7 women failed screening: 3 women had control cycle luteal phase serum P < 3 ng/mL; 3 women withdrew consent; and 1 potential subject was not enrolled because the study had enrolled the requisite number of subjects and was closed for enrollment

Participant milestones

Measure	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.
Overall Study STARTED	17
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	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.
Overall Study Early discontinuation from the study	3

Baseline Characteristics

Pharmacokinetic and Pharmacodynamic Study of Cyclofem

Baseline characteristics by cohort

Measure	Injection Cyclofem n=17 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	17 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	34.8 years STANDARD_DEVIATION 5.21 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	17 participants n=5 Participants

PRIMARY outcome

Timeframe: "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

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Medroxyprogesterone Acetate (MPA) Concentrations Day 1	0.00 ng/mL Standard Deviation 0.02
Medroxyprogesterone Acetate (MPA) Concentrations Day 29	0.27 ng/mL Standard Deviation 0.09
Medroxyprogesterone Acetate (MPA) Concentrations Day 57	0.43 ng/mL Standard Deviation 0.13
Medroxyprogesterone Acetate (MPA) Concentrations Day 85	0.44 ng/mL Standard Deviation 0.19

PRIMARY outcome

Timeframe: "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).

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Medroxyprogesterone Acetate (MPA) Pharmacokinetics AUC (0-84)	31.5029 ng*day/mL Standard Error 7.49456
Medroxyprogesterone Acetate (MPA) Pharmacokinetics AUC (0-28)	20.5831 ng*day/mL Standard Error 6.58448
Medroxyprogesterone Acetate (MPA) Pharmacokinetics AUC (0-inf)	33.4528 ng*day/mL Standard Error 8.23617

PRIMARY outcome

Timeframe: 85 days

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

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Medroxyprogesterone Acetate (MPA) Pharmacokinetics Cmax	1.311380 ng/mL Standard Error 0.437259

PRIMARY outcome

Timeframe: "Day 85"

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

Outcome measures

Measure	Injection Cyclofem n=15 Participants 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.
Medroxyprogesterone Acetate (MPA) Pharmacokinetics Tmax	4.1 day Standard Deviation 5.01

PRIMARY outcome

Timeframe: "Day 85"

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Medroxyprogesterone Acetate (MPA) Pharmacokinetics T1/2	16.9413 day Standard Deviation 7.49264

PRIMARY outcome

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

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

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Estradiol (E2) Concentrations Day 1	46 pg/mL Standard Deviation 18
Estradiol (E2) Concentrations Day 29	44 pg/mL Standard Deviation 19
Estradiol (E2) Concentrations Day 57	52 pg/mL Standard Deviation 22
Estradiol (E2) Concentrations Day 85	42 pg/mL Standard Deviation 17

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Estradiol (E2) Pharmacokinetics. AUC (0-inf)	3922.3365 pg*day/mL Standard Deviation 1019.80283
Estradiol (E2) Pharmacokinetics. AUC (0-28)	3289.6546 pg*day/mL Standard Deviation 888.56879

PRIMARY outcome

Timeframe: "Day 85"

Population: Tmax

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

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Tmax	3.3 day Standard Deviation 2.49

PRIMARY outcome

Timeframe: "Day 85"

Population: Tmax

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

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
T1/2 medroxyprogesterone acetate (MPA)	16.9413 day Standard Deviation 7.49264
T1/2 Estradiol (E2)	10.0960 day Standard Deviation 4.87120

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Injection Cyclofem n=17 Participants 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.
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration Day 18	17 participants
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration Day 106	1 participants
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration Day 131	1 participants
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration Day 21	17 participants
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration Day 103	0 participants
Number of Participants Who Achieved Ovulation Determined by Serum Progesterone Concentration Day 134	1 participants

Adverse Events

Injection Cyclofem

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Injection Cyclofem n=17 participants at risk 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.
Reproductive system and breast disorders Menorrhagia	41.2% 7/17 • Number of events 7 • The subjects were assessed for incidence of adverse events up to Day 92 (during the control and treatment period, and up to Day 134 (during the follow-up period) Toxicities and AEs were summarized by severity and relationship to treatment. Clinical laboratory parameters and vital signs were summarized as changes and shifts from baseline to final on treatment assignment and by clinically significant abnormalities. Vital signs during study drug dosing were summarized as changes from baseline.
Infections and infestations Vaginitis bacterial	11.8% 2/17 • Number of events 7 • The subjects were assessed for incidence of adverse events up to Day 92 (during the control and treatment period, and up to Day 134 (during the follow-up period) Toxicities and AEs were summarized by severity and relationship to treatment. Clinical laboratory parameters and vital signs were summarized as changes and shifts from baseline to final on treatment assignment and by clinically significant abnormalities. Vital signs during study drug dosing were summarized as changes from baseline.

Additional Information

Dr. Shravanti Bhowmik

SPARC

Phone: 02266455645

Email: shravanti.bhowmik@sparcmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place