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

NCT01258660 | Completed Phase 1 Results

• 3 other identifiers: 915092006-003522-29309763
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• 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)

  The Area under the curve (AUC) is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.

  up to 24 weeks of treatment

• Area Under the Curve From Time 0 to 24 Weeks [AUC(0-24weeks)] for Plasma Folate and RBC (Red Blood Cell) Folate (Baseline Corrected)

  The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.

  up to 24 weeks of treatment

• Proportion of Participants With RBC Folate Below 906 Nmol/L in the Yasmin + Metafolin Group in the Folate Elimination Phase (Week 24 to 44)

  Proportion of participants with RBC folate below 906 nmol/L in the Yasmin + Metafolin group in the folate elimination phase (week 24 to 44)

  from week 24 to week 44

Secondary Outcomes (5)

• Folate Metabolite Pattern in Plasma at Baseline

  pre-treatment

• Folate Metabolite Pattern in Plasma at Cycle 3

  week 12

• Folate Metabolite Pattern in Plasma at Cycle 6

  week 24

• Homocysteine Concentrations in Plasma at Baseline and at the End of Treatment (Week 24) With Metafolin

  baseline and week 24

• Homocysteine Concentrations in Plasma at Baseline and at the End of Treatment (Week 24) With Folic Acid

  baseline, and up to 24 weeks of treatment

Study Arms (2)

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

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

Interventions

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

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

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

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, Bavaria, 89231, Germany

Location

Related Publications (1)

• 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.

  PMID: 23610531 RESULT

MeSH Terms

Interventions

drospirenone; levomefolate calcium; drospirenone and ethinyl estradiol combination; Folic Acid

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2010
• First Posted: December 13, 2010
• Study Start: December 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: September 20, 2013
• Results First Posted: May 13, 2011

Record last verified: 2013-09

Locations

DE (1)