Efficacy and Safety Study for an Oral Contraceptive Containing Folate

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the study drug is safe and effective

Detailed Description
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Acronym is used in result section: suspected/diagnosed (susp/diag)

Official Title
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Multi-Center, Randomized, Double-Blind Active-Controlled, Parallel Group Study to Investigate Plasma Folate, Red Blood Cell Folate and Homocysteine Levels During a 24 Week Oral Administration of an OC Containing Folate Compared to OC Alone

Conditions
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Neural Tube Defects, Contraception, Oral Contraceptives (OC)

Intervention / Treatment
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* Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate
* Drug: Drospirenone/Ethinylestradiol (Yaz)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Healthy women between 18 and 40 requesting oral contraception Exclusion Criteria: - The use of steroidal oral contraceptives, or any drug that could alter Oral Contraception metabolism will be prohibited during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)<br>1 tablet 0.020 mg EE/3.0 mg DRSP/0.451 mg L-5-MTHF as calcium salt given orally/daily for 24 days followed by 1 tablet 0.451 mg L-5-MTHF as calcium salt given orally/daily for 4 days over a time period of 24 weeks | Drug: Drospirenone/Ethinylestradiol/Methyltetrahydrofolate<br>* 0.020 mg ethinylestradiol with 3.0 mg drospirenone and 0.451 mg L-5-methyltetrahydrofolate (L-5-MTHF)<br>|
| Active Comparator: Drospirenone (DRSP)/Ethinylestradiol (EE)<br>1 tablet 0.020 mg EE/3.0 mg DRSP [YAZ] given orally/daily for 24 days followed by 1 placebo tablet given orally/daily for 4 days over a time period of 24 weeks | Drug: Drospirenone/Ethinylestradiol (Yaz)<br>* 0.020 mg ethinylestradiol with 3.0 mg drospirenone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Red Blood Cell (RBC) Folate Level at 24 Weeks | RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit | Week 24 | 
| Plasma Folate Level at 24 Weeks | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Neural Tube Defect (NTD) Risk Reduction at Week 24 | The mean NTD risk reduction evaluated as the change from Baseline to Week 24 in NTD risk based on the formula of Daly et al (J Amer Med Assoc 1995;274(21):1698-702); NTD risk=exp (1.6463-1.2193 x natural log [RBC folate]) where natural log [RBC folate] is the natural log of RBC folate measured in nmol/L; Change from Baseline to Week 24 in NTD risk=NTD risk at Week 24 - NTD risk at Baseline | Baseline and week 24 | 
| Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4 | RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit | baseline and up to week 4 | 
| Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8 | RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit | baseline and up to week 8 | 
| Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12 | RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit | baseline and up to week 12 | 
| Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16 | RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit | baseline and up to week 16 | 
| Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20 | RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit | baseline and up to week 20 | 
| Mean Change From Baseline in Plasma Folate Levels at Week 4 | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. | baseline and up to week 4 | 
| Mean Change From Baseline in Plasma Folate Levels at Week 8 | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. | baseline and up to week 8 | 
| Mean Change From Baseline in Plasma Folate Levels at Week 12 | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. | baseline and up to week 12 | 
| Mean Change From Baseline in Plasma Folate Levels at Week 16 | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. | baseline and up to week 16 | 
| Mean Change From Baseline in Plasma Folate Levels at Week 20 | Folate concentrations in plasma were determined by an appropriately validated microbiological assay. | baseline and up to week 20 | 
| Mean Change From Baseline in Plasma Homocysteine Levels at Week 4 | Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting. | baseline and up to week 4 | 
| Mean Change From Baseline in Plasma Homocysteine Levels at Week 8 | Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting. | baseline and up to week 8 | 
| Mean Change From Baseline in Plasma Homocysteine Levels at Week 12 | Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting. | baseline and up to week 12 | 
| Mean Change From Baseline in Plasma Homocysteine Levels at Week 16 | Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting. | baseline and up to week 16 | 
| Mean Change From Baseline in Plasma Homocysteine Levels at Week 20 | Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting. | baseline and up to week 20 | 
| Mean Change From Baseline in Plasma Homocysteine Levels at Week 24 | Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting. | baseline and up to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy women requesting contraception, Folic Acid