Safety and Efficacy of PROMETRIUM® Capsules in Induction of Secretory Conversion

• Sponsor: Solvay Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00160199
• Collaborator: (none)
• Enrollment: 240
• Locations: 42
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the efficacy and safety of 300 mg and 400 mg doses of PROMETRIUM® capsules in women of reproductive age with secondary amenorrhea

Condition or Disease	Intervention/Treatment	Phase
Secondary Amenorrhea	Drug: PROMETRIUM® 300 mg; Drug: PROMETRIUM® 400 mg	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Safety and Efficacy of PROMETRIUM® Capsules in Induction of Secretory Conversion of Endometrium and Withdrawal Bleeding in Subjects With Secondary Amenorrhea
• Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: PROMETRIUM® 300 mg; 300 mg (3x100mg capsules) by mouth once daily at bedtime for 10 days X 3 cycles
Active Comparator: 2	Drug: PROMETRIUM® 400 mg; 400 mg (4x100mg capsules) by mouth once daily at bedtime for 10 days X 3 cycles

Outcome Measures

Primary Outcome Measures

1. Secretory Conversion of the Endometrium [End of the study (Days 85)]

   Endometrial biopsy results were classified as : Secretory (Complete or partial), Non-secretory, Unable to determine or Unknown after an evaluation of morphologic criteria.

2. Number of Subjects With Withdrawal Bleeding [After first and second cycle (cycle=28 days)]

   This measure is the number of subjects with withdrawal bleeding using Last Observation Carried Forward (LOCF) after first and second cycle.

Secondary Outcome Measures

1. Maximum Intensity of Withdrawal Bleeding After Any Cycle [Duration of withdrawal bleed]

   The intensity of withdrawal bleeding was classified by: None, Spotting, Light, Moderate, Heavy

2. The Duration of Withdrawal Bleeding After the First Treatment Cycle [End of the first cycle of treatment (cycle=28 days)]

   The numbers of days the subjects actually bled after the end of the first treatment cycle.

3. The Duration of Withdrawal Bleeding After Second Treatment Cycle [End of the second cycle of treatment (cycle=28 days)]

   The numbers of days the subjects actually bled after the end of the second treatment cycle

4. Time to Withdrawal Bleeding After First Treatment Cycle [End of the first cycle of treatment (cycle=28 days)]

   The number of days between the first cycle of treatment and the withdrawal bleeding.

5. Time to Withdrawal Bleeding After Second Treatment Cycle [End of the second cycle of treatment (cycle=28 days)]

   The number of days between the second cycle of treatment and the withdrawal bleeding

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Women with secondary amenorrhea

• Normal serum Dehydroepiandrosterone (DHEA), prolactin, testosterone, Thyroid Stimulating Hormone (TSH) and thyroxine

Exclusion Criteria:

• Primary amenorrhea

• Other medical conditions resulting in amenorrhea (e.g. Asherman's syndrome)

• Peanut allergy

• Allergy to progestational steroids

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 29	Mobile	Alabama	United States
2	Site 41	Montgomery	Alabama	United States
3	Site 26	Tucson	Arizona	United States
4	Site 5	Jonesboro	Arkansas	United States
5	Site 39	Carmichael	California	United States
6	Site 17	Encinitas	California	United States
7	Site 10	San Diego	California	United States
8	Site 42	Avon	Connecticut	United States
9	Site 3	Groton	Connecticut	United States
10	Site 22	New Britian	Connecticut	United States
11	Site 9	Waterbury	Connecticut	United States
12	Site 37	West Hartford	Connecticut	United States
13	Site 14	Aventura	Florida	United States
14	Site 40	Clearwater	Florida	United States
15	Site 1	West Palm Beach	Florida	United States
16	Site 30	West Palm Beach	Florida	United States
17	Site 46	Atlanta	Georgia	United States
18	Site 43	Powder Springs	Georgia	United States
19	Site 36	Champaign	Illinois	United States
20	Site 12	Chicago	Illinois	United States
21	Site 6	Baton Rouge	Louisiana	United States
22	Site 7	Baltimore	Maryland	United States
23	Site 2	St. Louis	Missouri	United States
24	Site 16	Reno	Nevada	United States
25	Site 45	New York	New York	United States
26	Site 23	New Bern	North Carolina	United States
27	Site 15	Winston-Salem	North Carolina	United States
28	Site 28	Winston-Salem	North Carolina	United States
29	Site 33	Cincinnati	Ohio	United States
30	Site 32	Erie	Pennsylvania	United States
31	Site 47	Hershey	Pennsylvania	United States
32	Site 44	Philadelphia	Pennsylvania	United States
33	Site 38	Pottstown	Pennsylvania	United States
34	Site 13	Greenville	South Carolina	United States
35	Site 8	Conroe	Texas	United States
36	Site 11	Corpus Christi	Texas	United States
37	Site 27	Houston	Texas	United States
38	Site 34	Houston	Texas	United States
39	Site 24	San Antonio	Texas	United States
40	Site 35	Salt Lake City	Utah	United States
41	Site 19	Norfolk	Virginia	United States
42	Site 4	Seattle	Washington	United States

Sponsors and Collaborators

• Solvay Pharmaceuticals

Investigators

• Study Director: Global Clinical Director Solvay, Solvay Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00160199
• Other Study ID Numbers: S168.4.002
• First Posted: Sep 12, 2005
• Last Update Posted: Jul 7, 2010
• Last Verified: Jun 1, 2010

• Keywords provided by , ,: To collect additional data on 300 and 400 mg doses of PROMETRIUM in women with secondary amenorrhea
• Additional relevant MeSH terms: Neoplasm Metastasis; Amenorrhea; Progesterone

Study Results

Participant Flow

Recruitment Details	Subjects were recruited in 42 centers in US between November 2004 and February 2009. Before the randomization, subjects were evaluated for eligibility. In total 240 subjects were randomized.
Pre-assignment Detail	The Baseline characteristics are presented using the Full Analysis Sample (FAS) to be online with the Efficacy analysis results.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Period Title: Overall Study
STARTED	122	118
COMPLETED	98	81
NOT COMPLETED	24	37

Baseline Characteristics

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	107	99	206
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.2 (6.63)	28.7 (6.35)	29.0 (6.49)
Sex: Female, Male (Count of Participants)
Female	107 100%	99 100%	206 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	107 100%	99 100%	206 100%

Outcome Measures

1. Primary Outcome

Title	Secretory Conversion of the Endometrium
Description	Endometrial biopsy results were classified as : Secretory (Complete or partial), Non-secretory, Unable to determine or Unknown after an evaluation of morphologic criteria.
Time Frame	End of the study (Days 85)

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
Secretory	23 21.5%	28 28.3%
Non-Secretory	70 65.4%	53 53.5%
Unable to determine	7 6.5%	9 9.1%
Unknown	4 3.7%	2 2%

2. Primary Outcome

Title	Number of Subjects With Withdrawal Bleeding
Description	This measure is the number of subjects with withdrawal bleeding using Last Observation Carried Forward (LOCF) after first and second cycle.
Time Frame	After first and second cycle (cycle=28 days)

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
Number [participants]	93 86.9%	90 90.9%

3. Secondary Outcome

Title	Maximum Intensity of Withdrawal Bleeding After Any Cycle
Description	The intensity of withdrawal bleeding was classified by: None, Spotting, Light, Moderate, Heavy
Time Frame	Duration of withdrawal bleed

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
None	13 12.1%	8 8.1%
Spotting (Intermittent Staining)	10 9.3%	3 3%
Light (Slight amount-continuous staining)	18 16.8%	14 14.1%
Moderate (Modest amount-continuous staining)	25 23.4%	40 40.4%
Heavy (Large amount-heavy clots)	40 37.4%	33 33.3%

4. Secondary Outcome

Title	The Duration of Withdrawal Bleeding After the First Treatment Cycle
Description	The numbers of days the subjects actually bled after the end of the first treatment cycle.
Time Frame	End of the first cycle of treatment (cycle=28 days)

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
Mean (Standard Deviation) [Days]	4.0 (2.03)	3.8 (1.88)

5. Secondary Outcome

Title	The Duration of Withdrawal Bleeding After Second Treatment Cycle
Description	The numbers of days the subjects actually bled after the end of the second treatment cycle
Time Frame	End of the second cycle of treatment (cycle=28 days)

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
Mean (Standard Deviation) [Days]	3.5 (2.15)	3.8 (1.62)

6. Secondary Outcome

Title	Time to Withdrawal Bleeding After First Treatment Cycle
Description	The number of days between the first cycle of treatment and the withdrawal bleeding.
Time Frame	End of the first cycle of treatment (cycle=28 days)

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
Mean (Standard Deviation) [Days]	1.9 (1.89)	2.2 (1.81)

7. Secondary Outcome

Title	Time to Withdrawal Bleeding After Second Treatment Cycle
Description	The number of days between the second cycle of treatment and the withdrawal bleeding
Time Frame	End of the second cycle of treatment (cycle=28 days)

Outcome Measure Data

Analysis Population Description

The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.

Arm/Group Title	Prometrium 300 mg/Day	Prometrium 400 mg/Day
Arm/Group Description
Measure Participants	107	99
Mean (Standard Deviation) [Days]	1.6 (1.99)	2.21 (1.72)

Adverse Events

Time Frame	The adverse events presented were collected from start of drug treatment to the end of the treatment period.
Adverse Event Reporting Description	The safety analysis is presented on the safety sample meaning the number of patients who were randomized and received at least one dose of study medication.
Arm/Group Title	Prometrium 300 mg/Day		Prometrium 400 mg/Day
Arm/Group Description
All Cause Mortality
	Prometrium 300 mg/Day		Prometrium 400 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Prometrium 300 mg/Day		Prometrium 400 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/113 (1.8%)		1/107 (0.9%)
Nervous system disorders
Hydrocephalus	1/113 (0.9%)		0/107 (0%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/113 (0%)		1/107 (0.9%)
Reproductive system and breast disorders
Adnexa uteri mass	1/113 (0.9%)		0/107 (0%)
Other (Not Including Serious) Adverse Events
	Prometrium 300 mg/Day		Prometrium 400 mg/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/113 (63.7%)		70/107 (65.4%)
Gastrointestinal disorders
Flatulence Bloating and distension	6/113 (5.3%)		5/107 (4.7%)
Gastrointestinal and Abdominal Pains (excl oral and throat)	9/113 (8%)		6/107 (5.6%)
Nausea and Vomiting	15/113 (13.3%)		9/107 (8.4%)
General disorders
Asthenic conditions	11/113 (9.7%)		7/107 (6.5%)
Infections and infestations
Fungal infection NEC	9/113 (8%)		6/107 (5.6%)
Upper respiratory tract infections	13/113 (11.5%)		16/107 (15%)
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue signs and symptoms NEC	6/113 (5.3%)		5/107 (4.7%)
Nervous system disorders
Headaches NEC	13/113 (11.5%)		9/107 (8.4%)
Neurological signs and symptoms NEC	6/113 (5.3%)		8/107 (7.5%)
Reproductive system and breast disorders
Breast signs and symptoms	8/113 (7.1%)		5/107 (4.7%)
Skin and subcutaneous tissue disorders
Acnes	8/113 (7.1%)		7/107 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Independent analysis and/or publication of these data by the investigator or any member of his/her staff are not permitted without prior written consent of Solvay Pharmaceuticals,Inc. Written permission will be contingent on the review by Solvay Pharmaceuticals, Inc. of the statistical analysis and manuscript and providing for non-disclosure of Solvay Pharmaceuticals, Inc. confidential or proprietary information.