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Efficacy Study of a Cervical Pessary Containing Progesterone for the Prevention of Preterm Delivery (PCP002)

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ClinicalTrials.gov Identifier: NCT02225353
Recruitment Status : Completed
First Posted : August 26, 2014
Results First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
Laboratorios Andromaco S.A.
Information provided by (Responsible Party):
Grünenthal GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Preterm Birth
Interventions Drug: Progesterone Cervical Pessary 6.3 g
Drug: Progesterone 200 mg vaginal capsules
Drug: Progesterone Cervical Pessary 7.7 g
Enrollment 271
Recruitment Details The trial started on 02 Sep 2013 with the enrollment of the first participant and was completed on 13 Mar 2017 when the last participant completed the last follow-up examination according to the protocol. 271 participants signed and informed consent. All 271 were randomized and treated.
Pre-assignment Details  
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal. Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal. Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Period Title: Overall Study
Started 91 90 90
Completed 87 84 75
Not Completed 4 6 15
Reason Not Completed
Lost to Follow-up             0             1             3
Protocol Violation             4             5             12
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules Total
Hide Arm/Group Description Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal. Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal. Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant. Total of all reporting groups
Overall Number of Baseline Participants 91 90 90 271
Hide Baseline Analysis Population Description
Intent-to-treat.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 90 participants 90 participants 271 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
91
 100.0%
90
 100.0%
90
 100.0%
271
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 91 participants 90 participants 90 participants 271 participants
27.57  (6.50) 27.60  (6.20) 28.18  (5.16) 27.78  (5.97)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 90 participants 90 participants 271 participants
Female 91 90 90 271
Male NA [1]  NA [1]  NA [1]  NA [2] 
[1]
Male was an exclusion criterion
[2]
Total not calculated because data are not available (NA) in one or more arms.
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 90 participants 90 participants 271 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
91
 100.0%
90
 100.0%
90
 100.0%
271
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Chile Number Analyzed 91 participants 90 participants 90 participants 271 participants
91 90 90 271
Height  
Mean (Standard Deviation)
Unit of measure:  Meter
Number Analyzed 91 participants 90 participants 90 participants 271 participants
1.57  (0.06) 1.58  (0.06) 1.58  (0.05) 1.58  (0.05)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram
Number Analyzed 91 participants 90 participants 90 participants 271 participants
66.65  (13.36) 71.26  (14.06) 70.62  (12.73) 69.50  (13.50)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter
Number Analyzed 91 participants 90 participants 90 participants 271 participants
27.03  (4.92) 28.61  (5.45) 28.23  (4.56) 27.95  (5.01)
Medical History - Prior Preterm Birth  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 90 participants 90 participants 271 participants
55
  60.4%
55
  61.1%
50
  55.6%
160
  59.0%
Medical History - Prior Pregnancy Premature Rupture of Membrane  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 90 participants 90 participants 271 participants
24
  26.4%
20
  22.2%
17
  18.9%
61
  22.5%
1.Primary Outcome
Title Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation
Hide Description

To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery.

For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period.

The number of participants not giving birth before 32 weeks and 34 weeks are reported.

Time Frame Up to 36 weeks of gestational age
Hide Outcome Measure Data
Hide Analysis Population Description
271 participants comprised the Intention-to-treat analysis (ITT) population at baseline, 268 participants at gestation week 32, and 262 participants at gestation week 34.
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description:
Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.
Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Number of Participants Analyzed 91 90 90
Measure Type: Count of Participants
Unit of Measure: Participants
No birth before 32 weeks Number Analyzed 90 participants 90 participants 88 participants
73
  81.1%
71
  78.9%
67
  76.1%
No birth before 34 weeks Number Analyzed 89 participants 88 participants 85 participants
66
  74.2%
64
  72.7%
61
  71.8%
2.Secondary Outcome
Title Number of Participants With Premature Rupture of Membranes
Hide Description A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician.
Time Frame Up to 36 weeks of gestational age
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-Treat Population
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description:
Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.
Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Number of Participants Analyzed 91 90 90
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.1%
4
   4.4%
3
   3.3%
3.Secondary Outcome
Title Anatomical Feature: Length of the Uterine Cervix
Hide Description During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed.
Time Frame Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT).
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description:
Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.
Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Number of Participants Analyzed 91 90 90
Mean (Standard Deviation)
Unit of Measure: millimeter
Baseline Visit Number Analyzed 91 participants 89 participants 89 participants
28.69  (9.06) 29.62  (8.66) 28.44  (8.55)
Visit 2 Number Analyzed 82 participants 78 participants 76 participants
28.51  (8.30) 30.34  (7.63) 29.29  (10.37)
Visit 3 Number Analyzed 74 participants 75 participants 69 participants
27.54  (7.27) 29.06  (7.65) 30.76  (8.28)
Visit 4 Number Analyzed 69 participants 71 participants 64 participants
27.82  (7.12) 27.60  (7.91) 29.37  (8.16)
Visit 5 Number Analyzed 61 participants 67 participants 62 participants
27.53  (7.40) 26.55  (7.81) 28.63  (10.16)
Visit 6 Number Analyzed 41 participants 43 participants 41 participants
27.42  (7.62) 27.28  (9.36) 27.49  (8.32)
Visit 7 Number Analyzed 28 participants 24 participants 18 participants
30.43  (9.39) 27.95  (8.85) 28.83  (8.00)
Final Visit Number Analyzed 49 participants 47 participants 38 participants
22.98  (8.06) 25.07  (7.49) 23.64  (9.26)
4.Secondary Outcome
Title Anatomical Feature: Position of the Uterine Cervix
Hide Description During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus.
Time Frame Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT).
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description:
Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.
Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Number of Participants Analyzed 91 90 90
Mean (Standard Deviation)
Unit of Measure: degrees
Baseline Visit Number Analyzed 54 participants 58 participants 40 participants
114.54  (22.58) 112.59  (22.48) 112.85  (20.03)
Visit 2 Number Analyzed 43 participants 43 participants 31 participants
111.47  (23.33) 115.02  (19.56) 109.74  (23.56)
Visit 3 Number Analyzed 40 participants 39 participants 32 participants
110.81  (17.78) 109.83  (25.65) 115.36  (24.93)
Visit 4 Number Analyzed 38 participants 40 participants 28 participants
105.58  (21.35) 117.61  (18.63) 113.29  (26.20)
Visit 5 Number Analyzed 31 participants 32 participants 25 participants
108.99  (21.97) 115.50  (19.15) 113.26  (15.21)
Visit 6 Number Analyzed 17 participants 16 participants 15 participants
112.96  (17.41) 114.50  (21.61) 121.65  (15.89)
Visit 7 Number Analyzed 15 participants 14 participants 6 participants
118.93  (14.10) 110.51  (20.94) 124.37  (13.32)
Final Visit Number Analyzed 29 participants 26 participants 18 participants
104.30  (23.98) 113.42  (24.76) 115.44  (16.14)
5.Secondary Outcome
Title Acceptability and Tolerance of Use of the Cerclage Pessary
Hide Description

A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary.

Data from this questionnaire was not collected.

Time Frame Up to 36 weeks of gestational age
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were analyzed
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description:
Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.
Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Number of Adverse Events Related With the Use of Treatment
Hide Description The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness.
Time Frame Up to 36 weeks of gestational age
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT)
Arm/Group Title Progesterone Cervical Pessary (6.3 g) Progesterone Cervical Pessary (7.7 g) Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description:
Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.
Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.
Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Number of Participants Analyzed 91 90 90
Overall Number of Units Analyzed
Type of Units Analyzed: Number of adverse events
200 248 200
Measure Type: Number
Unit of Measure: events
AE related to use of treatment 31 22 2
Unexpected serious adverse events 1 2 0
Time Frame up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks).
Adverse Event Reporting Description Treatment emergent adverse events.
 
Arm/Group Title Progesterone Cervical Pessary 6.3 g Progesterone Cervical Pessary 7.7 g Progesterone 200 mg Vaginal Capsules
Hide Arm/Group Description

91 pregnant women with Progesterone Cervical Pessary

Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g

90 pregnant women with Progesterone Cervical Pessary

Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g

90 pregnant women using Progesterone 200 mg vaginal capsules daily

Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily

All-Cause Mortality
Progesterone Cervical Pessary 6.3 g Progesterone Cervical Pessary 7.7 g Progesterone 200 mg Vaginal Capsules
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/91 (0.00%)   0/90 (0.00%)   0/90 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Progesterone Cervical Pessary 6.3 g Progesterone Cervical Pessary 7.7 g Progesterone 200 mg Vaginal Capsules
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   36/91 (39.56%)   35/90 (38.89%)   33/90 (36.67%) 
Blood and lymphatic system disorders       
Anaemia  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Congenital, familial and genetic disorders       
Ventricular hypoplasia  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Multiple congenital anomalies  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
General disorders       
Pyrexia  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Hepatobiliary disorders       
Cholelithiasis  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Cholestasis  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Infections and infestations       
Breast abscess  1  0/91 (0.00%)  0/90 (0.00%)  2/90 (2.22%) 
Urinary tract infection  1  0/91 (0.00%)  0/90 (0.00%)  2/90 (2.22%) 
Asymptomatic bacteriuria  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Bacterial vaginosis  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Pyelonephritis acute  1  3/91 (3.30%)  0/90 (0.00%)  0/90 (0.00%) 
Bacteriuria  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Investigations       
Blood Pressure Increased  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Metabolism and nutrition disorders       
Diabetic Metabolic Decompensation  1  0/91 (0.00%)  4/90 (4.44%)  0/90 (0.00%) 
Musculoskeletal and connective tissue disorders       
Pelvic pain  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Pain in extremity  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Nervous system disorders       
Cerebral ventricle dilatation  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Foetal cerebrovascular disorder  1  1/91 (1.10%)  1/90 (1.11%)  0/90 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Cervical incompetence  1  1/91 (1.10%)  0/90 (0.00%)  3/90 (3.33%) 
Foetal death  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Foetal growth restriction  1  0/91 (0.00%)  2/90 (2.22%)  2/90 (2.22%) 
Oligohydramnios  1  0/91 (0.00%)  2/90 (2.22%)  1/90 (1.11%) 
Preeclampsia  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Premature rupture of membranes  1  0/91 (0.00%)  4/90 (4.44%)  3/90 (3.33%) 
Threatened labour  1  1/91 (1.10%)  2/90 (2.22%)  1/90 (1.11%) 
Gestational hypertension  1  2/91 (2.20%)  0/90 (0.00%)  0/90 (0.00%) 
Haemorrhage in pregnancy  1  3/91 (3.30%)  1/90 (1.11%)  1/90 (1.11%) 
Polihidroamnios  1  2/91 (2.20%)  0/90 (0.00%)  0/90 (0.00%) 
Umbilical cord abnormality  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Premature labor  1  17/91 (18.68%)  6/90 (6.67%)  2/90 (2.22%) 
Foetal hypokinesia  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
HELLP syndrome  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Uterine contractions during pregnancy  1  1/91 (1.10%)  2/90 (2.22%)  0/90 (0.00%) 
Psychiatric disorders       
Drug use disorder  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Renal and urinary disorders       
Proteinuria  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Hydronephrosis  1  0/91 (0.00%)  2/90 (2.22%)  0/90 (0.00%) 
Renal Colic  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Reproductive system and breast disorders       
Shortened cervix  1  10/91 (10.99%)  9/90 (10.00%)  19/90 (21.11%) 
Pelvic pain  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Vaginal erosion  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Vaginal infection NOS  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Coital bleeding  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Cervix haemorrhage uterine  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Uterine haemorrhage  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Vascular disorders       
Hypertensive crisis  1  0/91 (0.00%)  1/90 (1.11%)  1/90 (1.11%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Progesterone Cervical Pessary 6.3 g Progesterone Cervical Pessary 7.7 g Progesterone 200 mg Vaginal Capsules
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   77/91 (84.62%)   73/90 (81.11%)   65/90 (72.22%) 
Blood and lymphatic system disorders       
Anaemia  1  11/91 (12.09%)  5/90 (5.56%)  5/90 (5.56%) 
Cardiac disorders       
Sinus tachycardia  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Congenital, familial and genetic disorders       
Congenital uterine anomaly  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Ear and labyrinth disorders       
Vertigo  1  0/91 (0.00%)  0/90 (0.00%)  2/90 (2.22%) 
Endocrine disorders       
Hypothyroidism  1  1/91 (1.10%)  4/90 (4.44%)  1/90 (1.11%) 
Gastrointestinal disorders       
Abdominal pain  1  1/91 (1.10%)  3/90 (3.33%)  2/90 (2.22%) 
Abdominal pain lower  1  3/91 (3.30%)  1/90 (1.11%)  3/90 (3.33%) 
Abdominal pain upper  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Constipation  1  5/91 (5.49%)  4/90 (4.44%)  2/90 (2.22%) 
Dental caries  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Diarrhoea  1  5/91 (5.49%)  3/90 (3.33%)  2/90 (2.22%) 
Dyspepsia  1  1/91 (1.10%)  0/90 (0.00%)  3/90 (3.33%) 
Flatulence  1  2/91 (2.20%)  0/90 (0.00%)  0/90 (0.00%) 
Gastritis  1  2/91 (2.20%)  1/90 (1.11%)  1/90 (1.11%) 
Gastrooesophageal reflux disease  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Haemorrhoids  1  2/91 (2.20%)  0/90 (0.00%)  0/90 (0.00%) 
Hyperchlorhydria  1  3/91 (3.30%)  3/90 (3.33%)  1/90 (1.11%) 
Nausea  1  0/91 (0.00%)  1/90 (1.11%)  1/90 (1.11%) 
Vomiting  1  2/91 (2.20%)  7/90 (7.78%)  2/90 (2.22%) 
Faecaloma  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Duodenogastric reflux  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
General disorders       
Oedema peripheral  1  3/91 (3.30%)  1/90 (1.11%)  3/90 (3.33%) 
Hepatobiliary disorders       
Cholelithiasis  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Cholestasis  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Immune system disorders       
Hypersensitivity  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Infections and infestations       
Bacterial vaginosis  1  14/91 (15.38%)  5/90 (5.56%)  2/90 (2.22%) 
Bronchitis  1  2/91 (2.20%)  3/90 (3.33%)  0/90 (0.00%) 
Cervicitis  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Fungal infection  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Gastrenteritis  1  0/91 (0.00%)  1/90 (1.11%)  1/90 (1.11%) 
Herpes zoster  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Influenza  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Pharyngitis  1  1/91 (1.10%)  2/90 (2.22%)  1/90 (1.11%) 
Pneumonia  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Sinusitis  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Tonsillitis  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Urinary tract infection  1  12/91 (13.19%)  11/90 (12.22%)  6/90 (6.67%) 
Vaginal infection  1  3/91 (3.30%)  0/90 (0.00%)  1/90 (1.11%) 
Vaginitis gardnerella  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Viral pharyngitis  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Viral upper respiratory tract infection  1  11/91 (12.09%)  7/90 (7.78%)  8/90 (8.89%) 
Vulvovaginal candidasis  1  3/91 (3.30%)  1/90 (1.11%)  4/90 (4.44%) 
Vulvovaginitis  1  13/91 (14.29%)  6/90 (6.67%)  11/90 (12.22%) 
Tooth infection  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Gynaecological chlamydia infection  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Ureaplasma infection  1  2/91 (2.20%)  2/90 (2.22%)  2/90 (2.22%) 
Mycoplasma infection  1  0/91 (0.00%)  2/90 (2.22%)  0/90 (0.00%) 
Vulvovaginal mycotic infection  1  16/91 (17.58%)  11/90 (12.22%)  10/90 (11.11%) 
Vaginitis chlamydial  1  1/91 (1.10%)  1/90 (1.11%)  0/90 (0.00%) 
Injury, poisoning and procedural complications       
Arthropod bite  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Fall  1  2/91 (2.20%)  1/90 (1.11%)  0/90 (0.00%) 
Thermal burn  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Tooth fracture  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Investigations       
Amniocentesis abnormal  1  0/91 (0.00%)  0/90 (0.00%)  2/90 (2.22%) 
Ultrasound uterus  1  1/91 (1.10%)  1/90 (1.11%)  0/90 (0.00%) 
Ultrasound uterus abnormal  1  1/91 (1.10%)  1/90 (1.11%)  1/90 (1.11%) 
Ureaplasma test positive  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Mycoplasma test positive  1  1/91 (1.10%)  1/90 (1.11%)  0/90 (0.00%) 
Foetal renal imaging abnormal  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Metabolism and nutrition disorders       
Diabetic metabolic decompensation  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/91 (1.10%)  0/90 (0.00%)  1/90 (1.11%) 
Back pain  1  4/91 (4.40%)  6/90 (6.67%)  2/90 (2.22%) 
Coccydynia  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Muscle spasms  1  0/91 (0.00%)  2/90 (2.22%)  2/90 (2.22%) 
Myalgia  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Pubic pain  1  5/91 (5.49%)  1/90 (1.11%)  6/90 (6.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Vulvovaginal warts  1  0/91 (0.00%)  0/90 (0.00%)  2/90 (2.22%) 
Nervous system disorders       
Carpal tunnel syndrome  1  1/91 (1.10%)  1/90 (1.11%)  1/90 (1.11%) 
Dizziness  1  0/91 (0.00%)  1/90 (1.11%)  1/90 (1.11%) 
Facial paralysis  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Headache  1  8/91 (8.79%)  2/90 (2.22%)  12/90 (13.33%) 
Tension headache  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Pregnancy, puerperium and perinatal conditions       
Gestational diabetes  1  6/91 (6.59%)  11/90 (12.22%)  7/90 (7.78%) 
Haemorrhage in pregnancy  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Polyhydramnios  1  3/91 (3.30%)  4/90 (4.44%)  2/90 (2.22%) 
Premature labour  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Premature rupture of membranes  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Threatened labour  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Uterine hypotonus  1  1/91 (1.10%)  1/90 (1.11%)  3/90 (3.33%) 
Umbilical cord abnormaility  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Uterine contractions during pregnancy  1  11/91 (12.09%)  12/90 (13.33%)  9/90 (10.00%) 
Uterine contractions abnormal  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Foetal hypokinesia  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Gestational hypertension  1  1/91 (1.10%)  2/90 (2.22%)  1/90 (1.11%) 
Uterine irritability  1  1/91 (1.10%)  2/90 (2.22%)  0/90 (0.00%) 
Psychiatric disorders       
Insomnia  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Renal and urinary disorders       
Dysuria  1  2/91 (2.20%)  0/90 (0.00%)  1/90 (1.11%) 
Pollakiuria  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Urinary incontinence  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Bladder spasm  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Reproductive system and breast disorders       
Ovarian cyst  1  2/91 (2.20%)  0/90 (0.00%)  0/90 (0.00%) 
Pelvic pain  1  12/91 (13.19%)  6/90 (6.67%)  11/90 (12.22%) 
Pruritus genital  1  0/91 (0.00%)  3/90 (3.33%)  1/90 (1.11%) 
Uterine haemorrhage  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Vaginal discharge  1  16/91 (17.58%)  22/90 (24.44%)  2/90 (2.22%) 
Vaginal haemorrhage  1  3/91 (3.30%)  3/90 (3.33%)  1/90 (1.11%) 
Vuvovaginal pruritus  1  1/91 (1.10%)  0/90 (0.00%)  1/90 (1.11%) 
Cervix haemorrhage uterine  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Vulvovaginal discomfort  1  1/91 (1.10%)  1/90 (1.11%)  0/90 (0.00%) 
Genital discharge  1  4/91 (4.40%)  0/90 (0.00%)  1/90 (1.11%) 
Vaginal erosion  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Cervix oedena  1  1/91 (1.10%)  0/90 (0.00%)  0/90 (0.00%) 
Shortened cervix  1  0/91 (0.00%)  1/90 (1.11%)  2/90 (2.22%) 
Vulvovaginal pain  1  2/91 (2.20%)  4/90 (4.44%)  0/90 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Bronchospasm  1  0/91 (0.00%)  0/90 (0.00%)  1/90 (1.11%) 
Productive cough  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Skin and subcutaneous tissue disorders       
Dermatitis allergic  1  0/91 (0.00%)  0/90 (0.00%)  3/90 (3.33%) 
Dermatitis atopic  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Dermatitis contact  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Pruritus  1  1/91 (1.10%)  3/90 (3.33%)  1/90 (1.11%) 
Skin striae  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Utricaria  1  0/91 (0.00%)  1/90 (1.11%)  0/90 (0.00%) 
Pruritus allergic  1  0/91 (0.00%)  1/90 (1.11%)  1/90 (1.11%) 
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Name/Title: Director of Clinical Trials
Organization: Grünenthal GmbH
Phone: +49 241 569 3223
Responsible Party: Grünenthal GmbH
ClinicalTrials.gov Identifier: NCT02225353     History of Changes
Other Study ID Numbers: EC12012/10IEI-9339
First Submitted: August 4, 2014
First Posted: August 26, 2014
Results First Submitted: March 5, 2018
Results First Posted: October 23, 2018
Last Update Posted: October 23, 2018