Trial Outcomes & Findings for Convenience and Safety of Assisted Reproductive Technology Procedures Using a Gonal-F Filled by Mass (Fbm) Liquid Formulation Applied by Pen for Ovulation Induction and In-vitro Fertilization (NCT NCT01183143)

Results Overview

Number of subjects who self-administered the IMP were presented in this outcome measure.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

215 participants

Primary outcome timeframe

Up to 1 year

Results posted on

2018-04-06

Participant Flow

Participant milestones

Participant milestones
Measure	GONAL-f® GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Overall Study STARTED	215
Overall Study Intention to Treat (ITT) Population	204
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	150

Reasons for withdrawal

Reasons for withdrawal
Measure	GONAL-f® GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Overall Study Protocol Violation	115
Overall Study Withdrawal by Subject	19
Overall Study Subject Questionnaires not returned	5
Overall Study Subjects enrolled, but not treated	11

Baseline Characteristics

Convenience and Safety of Assisted Reproductive Technology Procedures Using a Gonal-F Filled by Mass (Fbm) Liquid Formulation Applied by Pen for Ovulation Induction and In-vitro Fertilization

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GONAL-f® n=204 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Age, Continuous	30.0 years STANDARD_DEVIATION 3.3 • n=93 Participants
Sex: Female, Male Female	204 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 1 year

Population: The ITT population included all the subjects who received at least 1 dose of the IMP.

Number of subjects who self-administered the IMP were presented in this outcome measure.

Outcome measures

Outcome measures
Measure	GONAL-f® n=204 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Number of Subjects Who Self-administered the Investigational Medicinal Product (IMP)	159 subjects

SECONDARY outcome

Timeframe: Up to 1 year

Population: The ITT population included all the subjects who received at least 1 dose of the IMP. Here "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome.

Investigator evaluated the use of GONAL-f® prefilled pen in subjects as very satisfactory, satisfactory and average satisfaction.

Outcome measures

Outcome measures
Measure	GONAL-f® n=195 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator Very satisfactory	101 subjects
Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator Satisfactory	93 subjects
Global Evaluation of the GONAL-f® Prefilled Pen by the Investigator Average satisfaction	1 subjects

SECONDARY outcome

Timeframe: Up to 1 year

Population: The ITT population. Here "Overall Number of Subjects Analyzed" signifies those subjects who were evaluable for this outcome and "Number Analyzed" signifies those who were evaluable for the specified category.

Subjects were provided with the information on Pen's utilization via training session and in the form of information brochure. Subjects assessed both the methods using the following responses: satisfactory, satisfactory, unsatisfactory and very unsatisfactory.

Outcome measures

Outcome measures
Measure	GONAL-f® n=195 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Evaluation of the Information Given to the Subjects on the Pen's Utilization Training Session: Very satisfactory	89 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Training Session: Satisfactory	95 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Training Session: Unsatisfactory	5 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Training Session: Very unsatisfactory	1 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Information brochure: Very satisfactory	95 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Information brochure: Satisfactory	89 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Information brochure: Unsatisfactory	9 subjects
Evaluation of the Information Given to the Subjects on the Pen's Utilization Information brochure: Very unsatisfactory	2 subjects

SECONDARY outcome

Timeframe: Up to 1 year

Population: The ITT population included all the subjects who received, at least 1 dose of the IMP.

Stimulation duration was defined as the duration (in days) for which subjects underwent GONAL-f® treatment.

Outcome measures

Outcome measures
Measure	GONAL-f® n=204 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Duration of Ovarian Stimulation With GONAL-f®	10 days Interval 3.0 to 26.0

SECONDARY outcome

Timeframe: End of Stimulation period (up to a maximum 26 days)

Population: The ITT population included all the subjects who received at least 1 dose of the IMP. Here "Number of Participants Analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	GONAL-f® n=119 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Mean Number of Embryos Transferred	1.8 embryos Standard Deviation 0.7

SECONDARY outcome

Timeframe: Up to 26 days

Population: The ITT population included all the subjects who received at least 1 dose of the IMP.

Outcome measures

Outcome measures
Measure	GONAL-f® n=204 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Total and Average Daily Dose of GONAL-f® Total dose	1527 International Units (IU) Standard Deviation 964
Total and Average Daily Dose of GONAL-f® Daily dose	149.5 International Units (IU) Standard Deviation 75.9

SECONDARY outcome

Timeframe: Up to 20 Weeks of Gestation

Population: The ITT population included all the subjects who received, at least 1 dose of the IMP. "Number of Participants Analyzed" signifies ITT (OI/IUI) subjects who were evaluable for this outcome measure.

Pregnancy rate was defined as the percentage of subjects with diagnosis of pregnancy, who underwent OI/IUI. Clinical pregnancy: Evidence of pregnancy by clinical or ultrasound parameters at 12 weeks after fertilization. Biochemical pregnancy: Evidence of conception based only on biochemical data in the serum or urine before ultrasound evidence of a gestational sac. Ongoing pregnancy was defined when the pregnancy had completed 20 weeks of gestation.

Outcome measures

Outcome measures
Measure	GONAL-f® n=85 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) Clinical pregnancy	16.5 Percentage of subjects Interval 8.6 to 24.4
Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) Biochemical pregnancy	16.5 Percentage of subjects Interval 8.6 to 24.4
Pregnancy Rate in Subjects Receiving Stimulation by Ovulation Induction (OI) or Artificial Insemination (IUI) Ongoing pregnancy	16.5 Percentage of subjects Interval 8.6 to 24.4

SECONDARY outcome

Timeframe: End of Gestation period, assessed up to a maximum of 1 year

Population: Per Protocol (PP) population was defined as the group of subjects who completed the study, having returned their completed questionnaire and who did not present any major protocol deviations.

Number of subjects whose stimulation with the IMP resulted in the birth of a baby were reported.

Outcome measures

Outcome measures
Measure	GONAL-f® n=181 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Number of Subjects With Live Birth	41 subjects

SECONDARY outcome

Timeframe: Up to 1 year

Population: ITT population included all the subjects who received at least 1 dose of the investigational medicinal product.

Local tolerance at the GONAL-f ® injection site was assessed for the presence of pain, swelling/welt, redness, itch and haematoma.

Outcome measures

Outcome measures
Measure	GONAL-f® n=204 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator Pain	32 subjects
Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator Swelling/welt	3 subjects
Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator Redness	34 subjects
Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator Itch	8 subjects
Number of Subjects With Local Tolerance at GONAL-f ® Injection Site as Assessed by Investigator Haematoma	41 subjects

SECONDARY outcome

Timeframe: Up to 1 year

Population: The tolerance analysis set included of all the subjects who were presented at the inclusion visit.

An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerged or worsened relative to baseline (i.e. present at the initial study visit) during a clinical study with an investigational product, regardless of causal relationship and even if no investigational product has been administered.

Outcome measures

Outcome measures
Measure	GONAL-f® n=215 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Number of Subjects With at Least 1 Adverse Event	36 subjects

SECONDARY outcome

Timeframe: Up to 1 year

Population: The tolerance analysis set included of all the subjects who were presented at the inclusion visit.

Outcome measures

Outcome measures
Measure	GONAL-f® n=215 Participants GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Number of Subjects Taking at Least 1 Concomitant Treatment	28 subjects

Adverse Events

GONAL-f®

Serious events: 6 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GONAL-f® n=215 participants at risk GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous NOS	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.93% 2/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Pregnancy, puerperium and perinatal conditions Placental, amniotic and cavity disorders	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Pregnancy, puerperium and perinatal conditions Uterine contractions during pregnancy	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Reproductive system and breast disorders Ovarian hyperstimulation syndrome	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Surgical and medical procedures Uterine dilation and curettage	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.

Other adverse events

Other adverse events
Measure	GONAL-f® n=215 participants at risk GONAL-f® was administered subcutaneously to subjects between Day 2 and Day 5 of their cycle with a starting dose of 75 International Units (IU) per day for subjects who underwent ovulation induction (OI)/ artificial insemination (IUI) and between 150 and 225 IU per day for subjects who underwent in-vitro fertilization (IVF). For subjects who underwent OI/ IUI the dose was increased by 37.5 IU after Day 14 up to Week 4 if no ovarian response was observed.
Gastrointestinal disorders Abdominal pain upper	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Gastrointestinal disorders Nausea	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
General disorders Asthenia	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
General disorders Injection site erythema	1.9% 4/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
General disorders Injection site haemorrhage	7.0% 15/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
General disorders Injection site pain	1.9% 4/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
General disorders Injection site pruritus	0.93% 2/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Infections and infestations Pelvic infection	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cyst	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous NOS	1.4% 3/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Reproductive system and breast disorders Metrorrhagia	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Reproductive system and breast disorders Ovarian hyperstimulation syndrome	1.9% 4/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Reproductive system and breast disorders Vulvovaginal pruritus	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Vascular disorders Haemorrhoids	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.
Vascular disorders Venous insufficiency	0.47% 1/215 As per the planned analysis, data was collected for the tolerance population (overall population) irrespective of the type of stimulation. The tolerance population consisted of all the subjects who were presented at the inclusion visit.

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