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Efficacy and Safety Study for an Oral Contraceptive Containing Folate

Primary Purpose

Neural Tube Defects, Contraception, Oral Contraceptives (OC)

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Drospirenone/Ethinylestradiol/Methyltetrahydrofolate
Drospirenone/Ethinylestradiol (Yaz)
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Neural Tube Defects focused on measuring Healthy women requesting contraception, Folic Acid

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Orange County Clinical Trials
  • Medical Center for Clinical Research
  • SNBL Clinical Pharmacology Center, Inc.
  • Columbia University Medical Center
  • AAIPharma, Inc.
  • Lyndhurst Gynecologic Associates
  • Coastal Carolina Research Center
  • New Orleans Center for Clinical Research
  • NorthWest Kinetics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)

Drospirenone (DRSP)/Ethinylestradiol (EE)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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
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
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
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
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
Mean Change From Baseline in Plasma Folate Levels at Week 4
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Mean Change From Baseline in Plasma Folate Levels at Week 8
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Mean Change From Baseline in Plasma Folate Levels at Week 12
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Mean Change From Baseline in Plasma Folate Levels at Week 16
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Mean Change From Baseline in Plasma Folate Levels at Week 20
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 30, 2007
Last Updated
April 4, 2014
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00468481
Brief Title
Efficacy and Safety Study for an Oral Contraceptive Containing Folate
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether the study drug is safe and effective
Detailed Description
Acronym is used in result section: suspected/diagnosed (susp/diag)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neural Tube Defects, Contraception, Oral Contraceptives (OC)
Keywords
Healthy women requesting contraception, Folic Acid

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
385 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Drospirenone (DRSP)/Ethinylestradiol (EE)/Metafolin (MTHF)
Arm Type
Experimental
Arm Description
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
Arm Title
Drospirenone (DRSP)/Ethinylestradiol (EE)
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Drospirenone/Ethinylestradiol/Methyltetrahydrofolate
Intervention Description
0.020 mg ethinylestradiol with 3.0 mg drospirenone and 0.451 mg L-5-methyltetrahydrofolate (L-5-MTHF)
Intervention Type
Drug
Intervention Name(s)
Drospirenone/Ethinylestradiol (Yaz)
Intervention Description
0.020 mg ethinylestradiol with 3.0 mg drospirenone
Primary Outcome Measure Information:
Title
Red Blood Cell (RBC) Folate Level at 24 Weeks
Description
RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame
Week 24
Title
Plasma Folate Level at 24 Weeks
Description
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Mean Neural Tube Defect (NTD) Risk Reduction at Week 24
Description
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
Time Frame
Baseline and week 24
Title
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 4
Description
RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame
baseline and up to week 4
Title
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 8
Description
RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame
baseline and up to week 8
Title
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 12
Description
RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame
baseline and up to week 12
Title
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 16
Description
RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame
baseline and up to week 16
Title
Mean Change From Baseline in Red Blood Cell (RBC) Folate Levels at Week 20
Description
RBC folate=([whole blood folate*100]-[plasma folate*(100-hematocrit)])/hematocrit
Time Frame
baseline and up to week 20
Title
Mean Change From Baseline in Plasma Folate Levels at Week 4
Description
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame
baseline and up to week 4
Title
Mean Change From Baseline in Plasma Folate Levels at Week 8
Description
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame
baseline and up to week 8
Title
Mean Change From Baseline in Plasma Folate Levels at Week 12
Description
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame
baseline and up to week 12
Title
Mean Change From Baseline in Plasma Folate Levels at Week 16
Description
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame
baseline and up to week 16
Title
Mean Change From Baseline in Plasma Folate Levels at Week 20
Description
Folate concentrations in plasma were determined by an appropriately validated microbiological assay.
Time Frame
baseline and up to week 20
Title
Mean Change From Baseline in Plasma Homocysteine Levels at Week 4
Description
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame
baseline and up to week 4
Title
Mean Change From Baseline in Plasma Homocysteine Levels at Week 8
Description
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame
baseline and up to week 8
Title
Mean Change From Baseline in Plasma Homocysteine Levels at Week 12
Description
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame
baseline and up to week 12
Title
Mean Change From Baseline in Plasma Homocysteine Levels at Week 16
Description
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame
baseline and up to week 16
Title
Mean Change From Baseline in Plasma Homocysteine Levels at Week 20
Description
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame
baseline and up to week 20
Title
Mean Change From Baseline in Plasma Homocysteine Levels at Week 24
Description
Homocysteine concentrations in plasma were determined by Fluorescence Polarization Immunoassays (FPIA) using the Abbot AxSym analyzer in a clinical laboratory setting.
Time Frame
baseline and up to week 24

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
Facility Name
Orange County Clinical Trials
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Medical Center for Clinical Research
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
Facility Name
SNBL Clinical Pharmacology Center, Inc.
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
AAIPharma, Inc.
City
Morrisville
State/Province
North Carolina
ZIP/Postal Code
27560
Country
United States
Facility Name
Lyndhurst Gynecologic Associates
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Coastal Carolina Research Center
City
Mt. Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
New Orleans Center for Clinical Research
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
NorthWest Kinetics
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98418
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22067790
Citation
Bart S Sr, Marr J, Diefenbach K, Trummer D, Sampson-Landers C. Folate status and homocysteine levels during a 24-week oral administration of a folate-containing oral contraceptive: a randomized, double-blind, active-controlled, parallel-group, US-based multicenter study. Contraception. 2012 Jan;85(1):42-50. doi: 10.1016/j.contraception.2011.05.013. Epub 2011 Jul 13.
Results Reference
result
PubMed Identifier
23534865
Citation
Castano PM, Aydemir A, Sampson-Landers C, Lynen R. The folate status of reproductive-aged women in a randomised trial of a folate-fortified oral contraceptive: dietary and blood assessments. Public Health Nutr. 2014 Jun;17(6):1375-83. doi: 10.1017/S1368980013000864. Epub 2013 Mar 27.
Results Reference
result
PubMed Identifier
21903192
Citation
Taylor TN, Farkouh RA, Graham JB, Colligs A, Lindemann M, Lynen R, Candrilli SD. Potential reduction in neural tube defects associated with use of Metafolin-fortified oral contraceptives in the United States. Am J Obstet Gynecol. 2011 Nov;205(5):460.e1-8. doi: 10.1016/j.ajog.2011.06.048. Epub 2011 Jun 21.
Results Reference
result
PubMed Identifier
24105751
Citation
Campone M, Berton-Rigaud D, Joly-Lobbedez F, Baurain JF, Rolland F, Stenzl A, Fabbro M, van Dijk M, Pinkert J, Schmelter T, de Bont N, Pautier P. A double-blind, randomized phase II study to evaluate the safety and efficacy of acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy. Oncologist. 2013;18(11):1190-1. doi: 10.1634/theoncologist.2013-0061. Epub 2013 Oct 8.
Results Reference
result

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Efficacy and Safety Study for an Oral Contraceptive Containing Folate

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