Assessment of the Pharmacodynamic Effect on Plasma Folate and Red Blood Cell Folate and Comparison of the Folate Metabolites During the 24 Weeks of Treatment (Yasmin + Metafolin Versus Yasmin + Folic Acid) Followed by a 20 Week Elimination Phase of Folate

NCT ID: NCT01258660

Last Updated: 2013-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 172 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2008-01-31

Brief Summary

The purpose of this study is to examine and compare the uptake of levomefolate calcium (Metafolin, a registered vitamin supplement) and folic acid in the body during 24 weeks of treatment with a following folate elimination phase of 20 weeks in healthy volunteers seeking contraception. Yasmin (oral contraceptive containing drospirenone and ethinylestradiol) was co-administered over the entire period of 44 weeks.

Conditions

Contraception

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo

Combination EE/DRSP/ Metafolin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin\] given orally in a cyclic regimen for 24 weeks (6 cycles) in combination with folic acid placebo tablets (encapsulated). Each treatment cycle consisting of once daily hormone and Metafolin treatment for 21-days followed by once daily hormone free, Metafolin only regimen for 7 days. This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

Group Type: EXPERIMENTAL

EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo

Intervention Type: DRUG

Combination EE/DRSP/ Metafolin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin\] given orally in a cyclic regimen for 24 weeks (6 cycles) in combination with folic acid placebo tablets (encapsulated). Each treatment cycle consisting of once daily hormone and Metafolin treatment for 21-days followed by once daily hormone free, Metafolin only regimen for 7 days. This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid

Yasmin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)\] in combination with folic acid tablets 0.4 mg (encapsulated), given orally in a cyclic regimen for 24 weeks (6 cycles). Each treatment cycle providing once daily hormone and folic acid treatment for 21 days followed by once daily hormone free, folic acid only regimen for 7 days (encapsulated). This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

Group Type: EXPERIMENTAL

EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid

Intervention Type: DRUG

Yasmin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)\] in combination with folic acid tablets 0.4 mg (encapsulated), given orally in a cyclic regimen for 24 weeks (6 cycles). Each treatment cycle providing once daily hormone and folic acid treatment for 21 days followed by once daily hormone free, folic acid only regimen for 7 days (encapsulated). This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

Interventions

EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo

Combination EE/DRSP/ Metafolin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP) + 0.451 mg Metafolin\] given orally in a cyclic regimen for 24 weeks (6 cycles) in combination with folic acid placebo tablets (encapsulated). Each treatment cycle consisting of once daily hormone and Metafolin treatment for 21-days followed by once daily hormone free, Metafolin only regimen for 7 days. This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

Intervention Type: DRUG

EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid

Yasmin \[0.030 mg ethinylestradiol (EE) + 3 mg drospirenone (DRSP)\] in combination with folic acid tablets 0.4 mg (encapsulated), given orally in a cyclic regimen for 24 weeks (6 cycles). Each treatment cycle providing once daily hormone and folic acid treatment for 21 days followed by once daily hormone free, folic acid only regimen for 7 days (encapsulated). This phase was followed by 20 weeks (5 cycles) folate elimination phase consisting of oral administration of Yasmin alone.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 18-40 years.
• RBC folate > 317 nmol/L and < 906 nmol/L.
• At least 1 menstruation during the last 3 months before screening with the exception of women using progestin-only methods (injection, implant) or progestin-releasing intrauterine system (IUS).
• Negative pregnancy test at screening and at admission into the study.
• Healthy as confirmed by medical history and physical examination.
• Body mass index (BMI) of 18.5-30.0 kg/m2 .
• Volunteers that smoke less than 10 cigarettes per day can be included up to the age of 30 years.
• Adequate vitamin B12 status defined as plasma B12 concentrations ≥ 110 pmol/L.

Exclusion Criteria

• Regular intake of folic acid defined as > 100 μg folic acid/day in vitamin supplements or fortified food during the last 4 months.
• Treatment with the following medications, which has the potential of interfering with folate metabolism: cholestyramine, methotrexate, trimethoprim, sulfasalazine, salicylic acid, cotrimoxazol, antacids or antiepileptic drugs.
• Pregnancy, lactation (at least three cycles have to follow delivery, abortion, or lactation before start of treatment)
• Vascular or metabolic disease including existing or previous arterial thromboembolic diseases (myocardial infarction, stroke), existing or previous venous thromboembolic diseases (deep vein thrombosis, pulmonary embolism), and any condition which could increase the risk to suffer any of the above mentioned disorders
• Any disease or condition that could compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study medication.
• Any disease that may worsen under hormonal treatment or might interfere with the conduct of the study or the interpretation of the results (e.g., herpes gestationis or idiopathic icterus pregnancy; middle-ear deafness ; Sydenham's chorea, porphyria, disturbances in the bile flow.
• Liver diseases: Presence or history of severe hepatic diseases including benign or malignant tumors

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Nuvisan GmbH

Neu-Ulm, Bavaria, Germany

Countries

Germany

References

Diefenbach K, Trummer D, Ebert F, Lissy M, Koch M, Rohde B, Blode H. EE-drospirenone-levomefolate calcium versus EE-drospirenone + folic acid: folate status during 24 weeks of treatment and over 20 weeks following treatment cessation. Int J Womens Health. 2013 Apr 11;5:149-63. doi: 10.2147/IJWH.S37254. Print 2013.

Reference Type: RESULT

PMID: 23610531 (View on PubMed)

Other Identifiers

2006-003522-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

309763

Identifier Type: OTHER

Identifier Source: secondary_id

91509

Identifier Type: -

Identifier Source: org_study_id