Study to Evaluate Cycle Control With Norgestimate/Ethinyl Estradiol and Drospirenone/Ethinyl Estradiol in Healthy Sexually Active Females

Study Overview
=================
Brief Summary
-----------------
The purpose of this study in healthy sexually active females is to evaluate the cycle control with norgestimate/ethinyl estradiol versus drospirenone/ethinyl estradiol.

Detailed Description
-----------------
This is a randomized, open-label, active-controlled, multicenter study in healthy sexually active females to evaluate cycle control with norgestimate/ethinyl estradiol versus drospireneone/ethinyl estradiol. The Open-Label Treatment Phase will last for three 28-day cycles. Approximately 300 patients will be randomized in a 1:1 fashion according to a predetermined randomization schedule. Patients will be seen for a baseline visit (Visit 1) up to 35 days prior to dosing to obtain informed consent, have a physical examination including a breast exam, height and weight, vital signs, a Chlamydia test and a urine pregnancy test performed, and to give their medical history. Patients will be instructed to report bleeding data using an interactive voice response system (IVRS) based diary on a daily basis. Patients will be instructed to continue taking 1 pill each day for 3 cycles, record this information daily in the IVRS and to contact the study site if they have any questions or adverse events they would like to discuss. The final study visit (Visit 2) will occur on Day 8 after completing 3 cycles of study medication. Patients will be weighed, have vital signs performed, report any adverse events and or changes in concomitant medications, and complete the satisfaction questionnaire at the final visit. Safety will be assessed by physical examinations, adverse events, body weight and vital signs. Patients randomized to drospireneone/ethinyl estradiol and taking any medication that could increase serum potassium levels (as outlined in the Package Insert) will also have their potassium level checked during their first cycle of treatment (Days 15 to 28 of treatment). Three 28-day cycles of either norgestimate/ethinyl estradiol or drospirenone/ethinyl estradiol.

Official Title
-----------------
An Open Label Study to Evaluate Cycle Control With Ortho Tri-Cyclen Lo (Norgestimate/Ethinyl Estradiol) and Yaz (Drospirenone/Ethinyl Estradiol) in Healthy Sexually Active Females

Conditions
-----------------
Contraception

Intervention / Treatment
-----------------
* Drug: Norgestimate/ethinyl estradiol; Drospirenone/ethinyl estradiol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy females who want oral contraception No cervical or vaginal abnormalities on gynecological examination Negative Chlamydia test Pap smear without evidence of moderate or severe dysplasia or any malignancy within the preceding 12 months Negative urine pregnancy test conducted during Visit 1 One normal menstrual period in 35 days prior to Visit 1 Regular menstrual cycles (every 26-35 days) Last term pregnancy at least 42 days prior to Visit 1, and have had at least one normal menstrual period (typical in duration and amount of flow for the subject) since her last pregnancy Post-menarcheal and pre-menopausal At least one normal menstrual period (typical in duration and amount of flow for the subject) since having undergone uterines urgery or removal of an IUD, Norplant, DepoProvera or other hormonal injectables or implants. Exclusion Criteria: History or presence of disorders commonly accepted as contraindications to steroid hormonal therapy Previously discontinued ORTHO TRI-CYCLEN LO or YAZ due to breakthrough bleeding Pregnant or lactating Body mass index (BMI) of >40kg/m2 Clinical evidence of carcinoma or other malignancy (history of basal cell carcinoma of the skin is not exclusionary) History of alcohol or drug abuse in the investigator's judgment based on history and physical examination (within 12 months prior to Visit 1) Significant depression or psychiatric disease in the investigator's judgment based on history and physical examination which would result in an unreliable patient Patient deemed by the investigator to have questionable reliability in her ability to comply with the protocol and provide accurate information Have any medical condition or planned surgical procedure which, in the opinion of the investigator, may be exacerbated by treatment with study medication or a patient receiving any concurrent therapy that could be affected by treatment with study medication Disallowed therapies: currently taking therapeutic anticoagulants (e.g,. Coumadin, Heparin) or have a bleeding disorder (e.g. von Willebrand's Disease), DepoProvera or other hormonal injectables in the six months before Visit 1, currently have Norplant or other hormonal implants in place, or have had removal of Norplant within 60 days prior to Visit 1, used a steroid-containing IUD within 3 months prior to Visit 1 Or current use of an IUD Consistently elevated blood pressure defined as sitting systolic BP>140 mmHg or diastolic BP>90 mmHg Have an untreated thyroid disorder in the investigator's judgment based on history and physical examination unable to swallow solid, oral dosage forms whole with the aid of water (participants may not chew, divide, dissolve, or crush the study drug) Patients who in the opinion of the investigator should not be enrolled in the study based on the product labeling for ORTHO TRI-CYCLEN LO and YAZ including potential drug-drug interactions Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Norgestimate/ethinyl estradiol; Drospirenone/ethinyl estradiol|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days of Unscheduled Blood Loss - Cycle 1 | cycle control between treatment groups, cycle 1. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 1 (Day 8 to 21 for NGM/25mcg EE and day 8 to 24 for DRSP/20mcg EE) | 
| Number of Days of Unscheduled Blood Loss - Cycle 2 | cycle control between treatment groups, cycle 2. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 2 (Day 29 to 49 for NGM/25mcg EE and day 29 to 52 for DRSP/20mcg EE) | 
| Number of Days of Unscheduled Blood Loss - Cycle 3 | Number of Days of Unscheduled Blood Loss - Cycle 3. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 3 (Day 57 to 77 for NGM/25mcg EE and day 57 to 80 for DRSP/20mcg EE) | 
| Overall Number of Days of Unscheduled Blood Loss | cycle control between treatment groups, for three 28-day cycles. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 1 to Cycle 3 (Day 8 to Day 80) | 
| Number of Participants With the Indicated Number of Unscheduled Blood Loss Episodes | Unscheduled blood loss episodes are bounded on both sides by at least 1 non- bleeding day. | Cycle 1 to Cycle 3 (Day 8 to Day 80) | 
| Number of Days of Scheduled Blood Loss - Cycle 1 | cycle control between treatment groups, cycle 1. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Scheduled bleeding was defined as any bleeding that occurred while not taking active hormones, regardless of the duration of regimen. | Cycle 1 (Day 22 to 32 for NGM/25mcg EE and day 25 to 32 for DRSP/20mcg EE) | 
| Number of Days of Scheduled Blood Loss - Cycle 2 | cycle control between treatment groups, cycle 2. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Scheduled bleeding was defined as any bleeding that occurred while not taking active hormones, regardless of the duration of regimen. | Cycle 2 (Day 50 to 60 for NGM/25mcg EE and day 53 to 60 for DRSP/20mcg EE) | 
| Number of Days of Scheduled Blood Loss - Cycle 3 | cycle control between treatment groups, cycle 3. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Scheduled bleeding was defined as any bleeding that occurred while not taking active hormones, regardless of the duration of regimen. | Cycle 3 (Day 78 to 84 for NGM/25mcg EE and day 81 to 84 for DRSP/20mcg EE) | 
| Overall Number of Days of Scheduled Blood Loss | summary of the overall number of days of scheduled blood loss. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. Scheduled bleeding was defined as any bleeding that occurred while not taking active hormones, regardless of the duration of regimen. | Cycle 1 to Cycle 3 (Day 8 to Day 84) | 
| Number of Days of Total Blood Loss - Cycle 1 | cycle control between treatment groups, cycle 1. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. | Cycle 1 (Day 8 to Day 28) | 
| Number of Days of Total Blood Loss - Cycle 2 | cycle control between treatment groups, cycle 2. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. | Cycle 2 (day 29 to Day 56) | 
| Number of Days of Total Blood Loss - Cycle 3 | cycle control between treatment groups, cycle 3. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. | Cycle 3 (Day 57 to Day 84) | 
| Overall Number of Days of Total Blood Loss | cycle control between treatment groups, overall. Cycle control includes number of days of blood loss, incidence of blood loss, number of blood loss episodes, and blood loss flow intensity. | Cycle 1 to 3 (Day 8 to Day 84) | 
| Number of Participants With Unscheduled Bleeding Cycle 1 | Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 1 (Day 8 to 21 for NGM/25mcg EE and day 8 to 24 for DRSP/20mcg EE) | 
| Number of Participants With Unscheduled Bleeding Cycle 2 | Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 2 (Day 29 to 49 for NGM/25mcg EE and day 29 to 52 for DRSP/20mcg EE) | 
| Number of Participants With Unscheduled Bleeding Cycle 3 | Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 3 (Day 57 to 77 for NGM/25mcg EE and day 57 to 80 for DRSP/20mcg EE) | 
| Number of Participants With Breakthrough Bleeding/Spotting Cycle 1 | Breakthrough bleeding/spotting is any bleeding or spotting during active pills excluding days contiguous with withdrawal bleeding or continual withdrawal bleeding. | Cycle 1 (Day 8 to 21 for NGM/25mcg EE and day 8 to 24 for DRSP/20mcg EE) | 
| Number of Participants With Breakthrough Bleeding/Spotting Cycle 2 | Breakthrough bleeding/spotting is any bleeding or spotting during active pills excluding days contiguous with withdrawal bleeding or continual withdrawal bleeding. | Cycle 2 (Day 29 to 49 for NGM/25mcg EE and day 29 to 52 for DRSP/20mcg EE) | 
| Number of Participants With Breakthrough Bleeding/Spotting Cycle 3 | Unscheduled bleeding is any bleeding during active pills except days 1-4 of cycle 2 or 3 if contiguous with withdrawal bleeding and days 1-7 of the first cycle. | Cycle 3 (Day 57 to 77 for NGM/25mcg EE and day 57 to 80 for DRSP/20mcg EE) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction - Overall | patient satisfaction based on 5 questions during three 28-day cycles - Question 1 (Overall Satisfaction). On a scale of 1 to 5 where 1=Very satisfied and 5=Very dissatisfied. | Cycle 1 to Cycle 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
contraception, bleeding, cycle control