Clinical trial NCT01258660: 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
Official title: A Randomized, Double-blind, Double-dummy, 2-parallel Arms Clinical Trial to Assess the Pharmacodynamic Effect on Plasma Folate and Red Blood Cell Folate and to Compare the Profile of Circulating Folate Metabolites During 24 Weeks of Treatment With an Oral Contraceptive Containing Ethinylestradiol, Drospirenone and L-5-methyltetrahydrofolate (SH T04532A and SH T04532C) or Yasmin (SH T04532D and SH T04532PC) Co-administered With Folic Acid (SH K04532B) Followed by 20 Weeks of Open-label Treatment With Yasmin Only (Folate Elimination Phase) in Women Seeking Contraception
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Contraception
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-12-13
Enrollment: 172
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Area Under the Curve (AUC) From Time 0 to 24 Weeks [AUC(0-24weeks)] for Plasma Folate and RBC (Red Blood Cell) Folate (Baseline Uncorrected)
timeFrame: up to 24 weeks of treatment
measure: Area Under the Curve From Time 0 to 24 Weeks [AUC(0-24weeks)] for Plasma Folate and RBC (Red Blood Cell) Folate (Baseline Corrected)
timeFrame: up to 24 weeks of treatment
measure: Proportion of Participants With RBC Folate Below 906 Nmol/L in the Yasmin + Metafolin Group in the Folate Elimination Phase (Week 24 to 44)
timeFrame: from week 24 to week 44
Secondary outcomes:
measure: Folate Metabolite Pattern in Plasma at Baseline
timeFrame: pre-treatment
measure: Folate Metabolite Pattern in Plasma at Cycle 3
timeFrame: week 12
measure: Folate Metabolite Pattern in Plasma at Cycle 6
timeFrame: week 24
measure: Homocysteine Concentrations in Plasma at Baseline and at the End of Treatment (Week 24) With Metafolin
timeFrame: baseline and week 24
measure: Homocysteine Concentrations in Plasma at Baseline and at the End of Treatment (Week 24) With Folic Acid
timeFrame: baseline, and up to 24 weeks of treatment
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
state: Bayern
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.