Study of Safety and Efficacy of an Oral Contraceptive

• Sponsor: Warner Chilcott (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00477633
• Collaborator: (none)
• Enrollment: 1,700
• Locations: 63
• Arm: 1
• Duration (Months): 20.1
• Patients Per Site: 27
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This is a non-comparative study. the primary objective of the study is to assess the efficacy of a low dose oral contraceptive in the prevention of pregnancy. The secondary objectives are to assess the incidence of intracyclic bleeding; and to assess the safety and tolerability of the product.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: Norethindrone/ethinyl estradiol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1700 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: An Open Label Study of the Contraceptive Efficacy of Norethindrone and Ethinyl Estradiol.
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Norethindrone/ethinyl estradiol 1 tablet per day	Drug: Norethindrone/ethinyl estradiol; 1 tablet per day

Outcome Measures

Primary Outcome Measures

1. Pearl Index, 18-35 Years, MITT Population [13 cycles (28 days each), approximately 364 days]

   Pregnancy rate in women 18-35 years old, Pearl Index - number of pregnancies per 100 women-years of treatment

Secondary Outcome Measures

1. Mean Number of Days of Intracyclic Bleeding & Spotting, Cycles 2-13, MITT Population [12 cycles (28 days each), approximately 336 days]

2. Mean Median Duration (Days) of Intracyclic Bleeding & Spotting, Cycles 2-13, MITT Population [12 cycles (28 days each), approximately 336 days]

   Each IB episode has a unique duration, with 0, 1, 2, 3 or more episodes per cycle. To obtain "mean median duration" of episodes during a cycle, take the median duration of all episodes in each cycle. If there are no episodes in the cycle, then median duration is undefined/missing for that cycle. 1 episode - median duration = duration of that episode, 2 episodes - median duration = average of 2 durations, more than 2 episodes, calculated in usual way for median of an ordered set of numbers. Once median determined for each cycle/subject, the mean & SD of those quantities calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy Women

• Age 18-45

• At risk for pregnancy

• History of regular cycles

Exclusion Criteria:

• Contraindications for use of hormonal contraception

• Conditions which affect the absorption or metabolism of steroid hormones

• BMI>35

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Warner Chilcott Investigational Site	Chandler	Arizona	United States	85224
2	Warner Chilcott Investigational Site	Phoenix	Arizona	United States	85032
3	Warner Chilcott Investigational Site	Phoenix	Arizona	United States	85037
4	Warner Chilcott Investigational Site	Phoenix	Arizona	United States	85050
5	Warner Chilcott Investigational Site	Tempe	Arizona	United States	85282
6	Warner Chilcott Investigational Site	Tucson	Arizona	United States	85712
7	Warner Chilcott Investigational Site	San Diego	California	United States	92103
8	Warner Chilcott Investigational Site	San Diego	California	United States	92108
9	Warner Chilcott Investigational Site	Vista	California	United States	92083
10	Warner Chilcott Investigational Site	Castle Rock	Colorado	United States	80108
11	Warner Chilcott Investigational Site	Denver	Colorado	United States	80218
12	Warner Chilcott Investigational Site	Lakewood	Colorado	United States	80228
13	Warner Chilcott Investigational Site	Boynton Beach	Florida	United States	33472
14	Warner Chilcott Investigational Site	Brooksville	Florida	United States	34613
15	Warner Chilcott Investigational Site	Clearwater	Florida	United States	33759
16	Warner Chilcott Investigational Site	Gainesville	Florida	United States	32607
17	Warner Chilcott Investigational Site	Jacksonville	Florida	United States	32207
18	Warner Chilcott Investigational Site	Leesburg	Florida	United States	34748
19	Warner Chilcott Investigational Site	Miami	Florida	United States	33143
20	Warner Chilcott Investigational Site	Miami	Florida	United States	33186
21	Warner Chilcott Investigational Site	Pembroke Pines	Florida	United States	33021
22	Warner Chilcott Investigational Site	St. Petersburg	Florida	United States	33709
23	Warner Chilcott Investigational Site	West Palm Beach	Florida	United States	33401
24	Warner Chilcott Investigational Site	West Palm Beach	Florida	United States	33409
25	Warner Chilcott Investigational Site	Decatur	Georgia	United States	30034
26	Warner Chilcott Investigational Site	Champaign	Illinois	United States	61820
27	Warner Chilcott Investigational Site	Peoria	Illinois	United States	61615
28	Warner Chilcott Investigational Site	Indianapolis	Indiana	United States	46250
29	Warner Chilcott Investigational Site	Arkansas City	Kansas	United States	67005
30	Warner Chilcott Investigational Site	Wichita	Kansas	United States	67207
31	Warner Chilcott Investigational Site	Lexington	Kentucky	United States	40509
32	Warner Chilcott Investigational Site	Louisville	Kentucky	United States	40291
33	Warner Chilcott Investigational Site	Amite	Louisiana	United States	70422
34	Warner Chilcott Investigational Site	Marrero	Louisiana	United States	70072
35	Warner Chilcott Investigational Site	Chaska	Minnesota	United States	55318
36	Warner Chilcott Investigational Site	Berlin	New Jersey	United States	08009
37	Warner Chilcott Investigational Site	Edison	New Jersey	United States	08817
38	Warner Chilcott Investigational Site	Lawrenceville	New Jersey	United States	08648
39	Warner Chilcott Investigational Site	Moorestown	New Jersey	United States	08051
40	Warner Chilcott Investigational Site	New York	New York	United States	10016
41	Warner Chilcott Investigational Site	Cary	North Carolina	United States	27511
42	Warner Chilcott Investigational Site	New Bern	North Carolina	United States	28562
43	Warner Chilcott Investigational Site	Raleigh	North Carolina	United States	27612
44	Warner Chilcott Investigational Site	Winston-Salem	North Carolina	United States	27103
45	Warner Chilcott Investigational Site	Cleveland	Ohio	United States	44122
46	Warner Chilcott Investigational Site	Oklahoma City	Oklahoma	United States	73112
47	Warner Chilcott Investigational Site	Medford	Oregon	United States	97504
48	Warner Chilcott Investigational Site	Philadelphia	Pennsylvania	United States	19114
49	Warner Chilcott Investigational Site	Pittsburgh	Pennsylvania	United States	15206
50	Warner Chilcott Investigational Site	Pottstown	Pennsylvania	United States	19464-3224
51	Warner Chilcott Investigational Site	Columbia	South Carolina	United States	29201
52	Warner Chilcott Investigational Site	Austin	Texas	United States	78748
53	Warner Chilcott Investigational Site	Austin	Texas	United States	78759
54	Warner Chilcott Investigational Site	Dallas	Texas	United States	75234
55	Warner Chilcott Investigational Site	Houston	Texas	United States	77030
56	Warner Chilcott Investigational Site	San Antonio	Texas	United States	78229
57	Warner Chilcott Investigational Site	Magna	Utah	United States	84044
58	Warner Chilcott Investigational Site	Salt Lake City	Utah	United States	84109
59	Warner Chilcott Investigational Site	Salt Lake City	Utah	United States	84121
60	Warner Chilcott Investigational Site	West Valley City	Utah	United States	84120
61	Warner Chilcott Investigational Site	Norfolk	Virginia	United States	23507
62	Warner Chilcott Investigational Site	Richmond	Virginia	United States	23233
63	Warner Chilcott Investigational Site	Virginia Beach	Virginia	United States	23456

Sponsors and Collaborators

• Warner Chilcott

Investigators

• Study Director: Herman Ellman, Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT00477633
• Other Study ID Numbers: PR-00207
• First Posted: May 24, 2007
• Last Update Posted: Apr 22, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by Warner Chilcott: Contraception
• Additional relevant MeSH terms: Ethinyl Estradiol; Norethindrone; Norethindrone Acetate; Estradiol

Study Results

Participant Flow

Recruitment Details	Recruitment began 21 Jun 2007

Arm/Group Title	Norethindrone/Ethinyl Estradiol Tablets
Arm/Group Description	1 tablet daily 0.8mg norethindrone(NE)/ 0.025 mg ethinyl estradiol (EE) tablets for 24 days of 28 day cycle followed by 4 days of placebo
Period Title: Overall Study
STARTED	1700
COMPLETED	991
NOT COMPLETED	709

Baseline Characteristics

Arm/Group Title	Norethindrone/Ethinyl Estradiol Tablets
Arm/Group Description	1 tablet daily 0.8mg norethindrone(NE)/ 0.025 mg ethinyl estradiol (EE) tablets for 24 days of 28 day cycle followed by 4 days of placebo
Overall Participants	1700
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.8 (7.1)
Age, Customized (participants) [Number]
Between 18 and 35 years	1251 73.6%
>35 years	319 18.8%
Sex: Female, Male (Count of Participants)
Female	1700 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	1700 100%

Outcome Measures

1. Primary Outcome

Title	Pearl Index, 18-35 Years, MITT Population
Description	Pregnancy rate in women 18-35 years old, Pearl Index - number of pregnancies per 100 women-years of treatment
Time Frame	13 cycles (28 days each), approximately 364 days

Outcome Measure Data

Analysis Population Description

MITT Population, Subjects Aged 18-35 years

Arm/Group Title	Norethindrone/Ethinyl Estradiol Tablets
Arm/Group Description	1 tablet daily 0.8mg norethindrone(NE)/ 0.025 mg ethinyl estradiol (EE) tablets for 24 days of 28 day cycle followed by 4 days of placebo
Measure Participants	1251
Number (95% Confidence Interval) [Pearl Index]	1.903

2. Secondary Outcome

Title	Mean Number of Days of Intracyclic Bleeding & Spotting, Cycles 2-13, MITT Population
Time Frame	12 cycles (28 days each), approximately 336 days

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	Norethindrone/Ethinyl Estradiol Tablets
Arm/Group Description	1 tablet daily 0.8mg norethindrone(NE)/ 0.025 mg ethinyl estradiol (EE) tablets for 24 days of 28 day cycle followed by 4 days of placebo
Measure Participants	1570
Mean (Standard Deviation) [Days]	1.19 (1.79)

3. Secondary Outcome

Title	Mean Median Duration (Days) of Intracyclic Bleeding & Spotting, Cycles 2-13, MITT Population
Description	Each IB episode has a unique duration, with 0, 1, 2, 3 or more episodes per cycle. To obtain "mean median duration" of episodes during a cycle, take the median duration of all episodes in each cycle. If there are no episodes in the cycle, then median duration is undefined/missing for that cycle. 1 episode - median duration = duration of that episode, 2 episodes - median duration = average of 2 durations, more than 2 episodes, calculated in usual way for median of an ordered set of numbers. Once median determined for each cycle/subject, the mean & SD of those quantities calculated.
Time Frame	12 cycles (28 days each), approximately 336 days

Outcome Measure Data

Analysis Population Description

MITT Population

Arm/Group Title	Norethindrone/Ethinyl Estradiol Tablets
Arm/Group Description	1 tablet daily 0.8mg norethindrone(NE)/ 0.025 mg ethinyl estradiol (EE) tablets for 24 days of 28 day cycle followed by 4 days of placebo
Measure Participants	1570
Mean (Standard Deviation) [Days]	3.52 (2.14)

Adverse Events

Time Frame	21 Jun 2007 thru 23 Jan 2009
Arm/Group Title	Norethindrone/Ethinyl Estradiol Tablets
Arm/Group Description	1 tablet daily 0.8mg norethindrone(NE)/ 0.025 mg ethinyl estradiol (EE) tablets for 24 days of 28 day cycle followed by 4 days of placebo
All Cause Mortality
	Norethindrone/Ethinyl Estradiol Tablets
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Norethindrone/Ethinyl Estradiol Tablets
	Affected / at Risk (%)	# Events
Total	20/1677 (1.2%)
Cardiac disorders
Angina pectoris	1/1677 (0.1%)	1
Gastrointestinal disorders
Vomiting	1/1677 (0.1%)	1
Abdominal Pain	2/1677 (0.1%)	2
Diarrhea Hemorrhagic	1/1677 (0.1%)	1
Colitis Ischemic	1/1677 (0.1%)	1
General disorders
Chest Pain	2/1677 (0.1%)	2
Infections and infestations
Mengitis, Viral	1/1677 (0.1%)	1
Appendicitis	1/1677 (0.1%)	1
Staphylococcal Infection	1/1677 (0.1%)	1
Injury, poisoning and procedural complications
Multiple Fractures	1/1677 (0.1%)	1
Cervical Vertebral Fracture	1/1677 (0.1%)	1
Investigations
Blood Pressure Increased	1/1677 (0.1%)	1
Metabolism and nutrition disorders
Dehydration	1/1677 (0.1%)	1
Musculoskeletal and connective tissue disorders
Flank Pain	1/1677 (0.1%)	1
Intervertebral disc protrusion	1/1677 (0.1%)	1
Nervous system disorders
Headache	1/1677 (0.1%)	1
Psychiatric disorders
Depression	1/1677 (0.1%)	1
Suicidal Ideation	2/1677 (0.1%)	2
Anxiety	1/1677 (0.1%)	1
Major Depression	1/1677 (0.1%)	1
Reproductive system and breast disorders
Cervical Dysplasia	1/1677 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/1677 (0.1%)	1
Respiratory Tract Infection	1/1677 (0.1%)	1
Surgical and medical procedures
Cholescystectomy	1/1677 (0.1%)	1
Intervertebral disc operation	1/1677 (0.1%)	1
Vascular disorders
Hypertension	1/1677 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Norethindrone/Ethinyl Estradiol Tablets
	Affected / at Risk (%)	# Events
Total	1179/1677 (70.3%)
Gastrointestinal disorders
Nausea	102/1677 (6.1%)	102
Vomiting	46/1677 (2.7%)	46
Diarrhoea	34/1677 (2%)	34
Gastroenteritis Viral	34/1677 (2%)	34
Infections and infestations
Bronchitis	46/1677 (2.7%)	46
Fungal Infection	35/1677 (2.1%)	35
Investigations
Laboratory Test Abnormal	48/1677 (2.9%)	48
Weight Increased	38/1677 (2.3%)	38
Smear Cervix Abnormal	36/1677 (2.1%)	36
Nervous system disorders
Headache	80/1677 (4.8%)	80
Psychiatric disorders
Anxiety	36/1677 (2.1%)	36
Renal and urinary disorders
Urinary Tract Infection	80/1677 (4.8%)	80
Reproductive system and breast disorders
Dysmenorrhoea	66/1677 (3.9%)	66
Vaginitis Bacterial	58/1677 (3.5%)	58
Vulvovaginal Mycotic Infection	52/1677 (3.1%)	52
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection	122/1677 (7.3%)	122
Nasopharyngitis	121/1677 (7.2%)	121
Sinusitis	91/1677 (5.4%)	91
Skin and subcutaneous tissue disorders
Acne	54/1677 (3.2%)	54

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.