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

Bayer

Status and phase: Completed; Phase 1

Conditions: Contraception

Treatments: Drug: EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo; Drug: EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid

Study type: Interventional

Funder types: Industry

Identifiers

NCT01258660

91509

309763 (Other Identifier)

2006-003522-29 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 172 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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172 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

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

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

Experimental group

Description:

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.

Treatment:

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