ContraceptionPhase 1NCT01258660
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
A Phase 1 study testing EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid in people with Contraception, run by Bayer at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception
- What is being tested?
- EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 172 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2006to Jan 2008
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placebo, EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EE 0.03 mg/DRSP 3 mg/Metafolin + folic acid placeboDrug
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 acidDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: EE 0.03 mg/DRSP 3 mg (Yasmin) + folic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
Measured: from week 24 to week 44
Secondary outcomes (5)
Folate Metabolite Pattern in Plasma at Baseline
Folate metabolite pattern in plasma at baseline
Measured: pre-treatment
Folate Metabolite Pattern in Plasma at Cycle 3
Folate metabolite pattern in plasma at cycle 3
Measured: week 12
Folate Metabolite Pattern in Plasma at Cycle 6
Folate metabolite pattern in plasma at cycle 6
Measured: week 24
Homocysteine Concentrations in Plasma at Baseline and at the End of Treatment (Week 24) With Metafolin
Homocysteine concentrations in plasma at baseline (median of baseline concentrations) and at the end of treatment (week 24) with Metafolin
Measured: baseline and week 24
Homocysteine Concentrations in Plasma at Baseline and at the End of Treatment (Week 24) With Folic Acid
Homocysteine concentrations in plasma at baseline (median of baseline concentrations) and at the end of treatment (week 24) with folic acid
Measured: baseline, and up to 24 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2010 (estimated)
- Study startDec 2006
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01258660
- Sponsor's protocol ID
- 91509
- Other IDs
- 2006-003522-29, 309763
- Status last verified
- Sep 2013
- First submitted
- 10 Dec 2010
- Last updated
- 20 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23610531