Trial Outcomes & Findings for Low-dose Gonal-f® in Ovulation Induction (NCT NCT01871532)

Results Overview

The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (\>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

24 participants

Primary outcome timeframe

Baseline up to 4 weeks

Results posted on

2016-08-11

Participant Flow

Participant milestones

Participant milestones
Measure	Low Dose Gonal-f Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Standard Low Dose Gonal-f Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Overall Study STARTED	12	12
Overall Study Subjects Received hCG Treatment	11	9
Overall Study COMPLETED	11	10
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Dose Gonal-f Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Standard Low Dose Gonal-f Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Low-dose Gonal-f® in Ovulation Induction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Dose Gonal-f n=12 Participants Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Standard Low Dose Gonal-f n=12 Participants Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Total n=24 Participants Total of all reporting groups
Age, Continuous	30.8 years STANDARD_DEVIATION 2.96 • n=5 Participants	29.5 years STANDARD_DEVIATION 3.75 • n=7 Participants	30.1 years STANDARD_DEVIATION 3.37 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 4 weeks

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (\>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 4 weeks

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

The bifollicular development was defined as the number of cycles with bifollicular development of only two follicles greater than or equal to 17 millimeter.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 4 weeks

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

The multifollicular development was defined as the number of cycles with multifollicular development of three or more follicles greater than or equal to 14 millimeter

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Ovulation was defined as a serum progesterone (P4 ) level greater than or equal to 10 nanogram per milliliter (ng/mL) or Clinical Pregnancy. Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 4 weeks

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 35-42 days post hCG administration

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 35-42 days post hCG administration

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning-identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 35-42 days post hCG administration

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 35-42 days post hCG administration

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Miscarriages were calculated per clinical pregnancy, and clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or confirmed by clinical signs of pregnancy. It excludes ectopic pregnancy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 42 days post hCG administration

Population: Safety population included all subjects who were randomised and received at least 1 Gonal-f injection.

OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications.

Outcome measures

Outcome measures
Measure	Low Dose Gonal-f n=12 Participants Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Standard Low Dose Gonal-f n=12 Participants Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)	0 subjects	0 subjects

SECONDARY outcome

Timeframe: Baseline up to 4 weeks

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 4 weeks

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 4

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline

Population: Data was not assessed since the study was terminated early due to the delay in providing additional study drug following a batch recall.

Outcome measures

Outcome data not reported

Adverse Events

Low Dose Gonal-f

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Standard Low Dose Gonal-f

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Low Dose Gonal-f n=12 participants at risk Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Standard Low Dose Gonal-f n=12 participants at risk Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/12	8.3% 1/12

Other adverse events

Other adverse events
Measure	Low Dose Gonal-f n=12 participants at risk Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.	Standard Low Dose Gonal-f n=12 participants at risk Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Gastrointestinal disorders Abdominal pain	0.00% 0/12	8.3% 1/12
Gastrointestinal disorders Abdominal tenderness	0.00% 0/12	8.3% 1/12
Gastrointestinal disorders Dry Mouth	0.00% 0/12	8.3% 1/12
Gastrointestinal disorders Nausea	8.3% 1/12	0.00% 0/12
General disorders Pain	0.00% 0/12	8.3% 1/12
Nervous system disorders Headache	8.3% 1/12	0.00% 0/12
Reproductive system and breast disorders Breast tenderness	0.00% 0/12	8.3% 1/12
Reproductive system and breast disorders Vaginal discharge	0.00% 0/12	8.3% 1/12

Additional Information

Merck KGaA Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER