Trial Outcomes & Findings for Phase 3 Trial to Evaluate the Efficacy and Safety of COL-1620 Vaginal Progesterone Gel (NCT NCT01863680)
NCT ID: NCT01863680
Last Updated: 2015-12-21
Results Overview
Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
178 participants
Primary outcome timeframe
Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])
Results posted on
2015-12-21
Participant Flow
First subject/Last subject (signed informed consent form \[ICF\]): 22 Jul 2013/02 Jun 2014; Study completed: 14 Oct 2014; Data base lock: 12 Nov 2014.
A total of 195 subjects were screened and 178 subjects were enrolled in the trial; 169 subjects started controlled ovarian stimulation (COS) treatment and 149 subjects received at least 1 dose of investigational medicinal product (IMP), 123 subjects have undergone in-vitro fertilization/ embryo transfer (IVF/ET).
Participant milestones
| Measure |
COL-1620
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using Gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Overall Study
STARTED
|
178
|
|
Overall Study
Subjects Started COS Treatment
|
169
|
|
Overall Study
Subjects Received hCG Injection
|
162
|
|
Overall Study
Subjects Received Study Drug
|
149
|
|
Overall Study
Subjects Who Have Undergone IVF/ET
|
123
|
|
Overall Study
COMPLETED
|
121
|
|
Overall Study
NOT COMPLETED
|
57
|
Reasons for withdrawal
| Measure |
COL-1620
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using Gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Overall Study
Adverse Event
|
17
|
|
Overall Study
Risk of OHSS
|
17
|
|
Overall Study
Spontaneous pregnancy
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Did not undergo IVF/ET
|
14
|
|
Overall Study
Other
|
6
|
Baseline Characteristics
Phase 3 Trial to Evaluate the Efficacy and Safety of COL-1620 Vaginal Progesterone Gel
Baseline characteristics by cohort
| Measure |
COL-1620
n=149 Participants
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro fertilization and embryo transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Age, Continuous
|
34.41 Years
STANDARD_DEVIATION 3.71 • n=5 Participants
|
|
Sex: Female, Male
Female
|
149 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])Population: The intention-to-treat subjects included all the subjects who underwent IVF/ET.
Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred.
Outcome measures
| Measure |
COL-1620
n=123 Participants
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Clinical Pregnancy Rate Per Embryo Transfer
|
28.5 Percentage of pregnancy/embryo transfer
|
SECONDARY outcome
Timeframe: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])Population: The intention-to-treat subjects included all the subjects who underwent IVF/ET.
Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS during Visit 6 (Week 5), but with a positive serum beta-hCG pregnancy test result at Visit 5 (Day 14+/-3). Biochemical pregnancy rate was calculated as the number of subjects who had no fetal sac observed during Visit 6 (Week 5) TVUS assessment or subjects who had a positive serum pregnancy test at Visit 5 (Day 14+/-3) and no data recorded at Visit 6 (Week 5) divided by the number of subjects who has at least 1 embryo transferred.
Outcome measures
| Measure |
COL-1620
n=123 Participants
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Biochemical Pregnancy Rate Per Embryo Transfer
|
7.3 Percentage of pregnancy/embryo transfer
|
SECONDARY outcome
Timeframe: Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3)Population: The PK analysis set included all subjects who had serum beta-hCG pregnancy test performed at Visit 5 (Day 14+/-3), who had two progesterone concentrations at Visit 2-2 and Visit 5, and who had no relevant problems for compliance of administration until Visit 5. "n" signifies the number of subjects who were evaluable in each category, respectively.
Two pharmacokinetic (PK) samples were collected per subject for the measurement of serum progesterone concentrations; 1st sample at Visit 2-2 (prior to hCG administration) and second sample during Visit 5 (Day 14+/-3, 7 hours after the morning of investigational medicinal product administration).
Outcome measures
| Measure |
COL-1620
n=121 Participants
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
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Serum Progesterone Level
Subjects with +ve serum beta-hCG: Visit 2-2 (n=44)
|
1.023 nanogram per milliliter (ng/mL)
Standard Deviation 0.414
|
|
Serum Progesterone Level
Subjects with +ve serum beta-hCG: Visit 5 (n=44)
|
61.508 nanogram per milliliter (ng/mL)
Standard Deviation 76.206
|
|
Serum Progesterone Level
Subjects with -ve serum beta-hCG: Visit 2-2 (n=77)
|
0.988 nanogram per milliliter (ng/mL)
Standard Deviation 0.471
|
|
Serum Progesterone Level
Subjects with -ve serum beta-hCG: Visit 5 (n=77)
|
7.765 nanogram per milliliter (ng/mL)
Standard Deviation 3.202
|
Adverse Events
COL-1620
Serious events: 5 serious events
Other events: 92 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
COL-1620
n=149 participants at risk
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Pregnancy, puerperium and perinatal conditions
Abortion threatened
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
2.7%
4/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
Other adverse events
| Measure |
COL-1620
n=149 participants at risk
The subjects were administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8% gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12 or until the confirmation of miscarriage or extra-uterine pregnancy, or a negative pregnancy test whichever was earlier.
Subjects had undergone conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation, follicle-stimulating hormone (FSH) or human chorionic gonadotropin (hCG).
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia of pregnancy
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Eye disorders
Asthenopia
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Abdominal distension
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
7.4%
11/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain lower
|
4.7%
7/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Anal fissure
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Ascites
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
8.1%
12/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
10/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Faeces soft
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
2.7%
4/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Cystitis
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Escherichia vaginitis
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Gastroenteritis viral
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Genital candidiasis
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Influenza
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
5.4%
8/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Vulvitis
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Infections and infestations
Vulvovaginal candidiasis
|
4.7%
7/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Foreign body
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Injury corneal
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Investigations
Urine ketone body present
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Nervous system disorders
Dizziness postural
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
2.7%
4/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Nervous system disorders
Migraine
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion threatened
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Pregnancy, puerperium and perinatal conditions
Haemorrhage in pregnancy
|
2.0%
3/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
|
6.0%
9/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy of unknown location
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Pregnancy, puerperium and perinatal conditions
Uterine contractions during pregnancy
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Renal and urinary disorders
Haematuria
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Renal and urinary disorders
Pollakiuria
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Cervical polyp
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
2.0%
3/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Haemorrhagic ovarian cyst
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Hyperreactio luteinalis
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Menometrorrhagia
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Ovarian cyst
|
4.0%
6/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Ovarian enlargement '
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
19.5%
29/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Vaginal discharge
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
2.7%
4/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Alopecia areata
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pityriasis rosea
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.67%
1/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
|
Vascular disorders
Hypotension
|
1.3%
2/149 • From the first dose of study drug administration up to Week 15
Safety analysis population included all the subjects who received at least one dose of study drug.
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The study as a whole will be published prior to any individual investigator publications. It is required that copies of all papers, abstracts, articles, etc. that contain study data are to be forward to the Sponsor for review 30 days prior to submission for publication.
- Publication restrictions are in place
Restriction type: OTHER