Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Estradiol Valerate/ Levomefolate Calcium · 5 trials · 4 indications
Dysmenorrheic pain was defined as pelvic pain during the menstrual/withdrawal bleeding episode and the 2 days before this episode. Baseline period: 2 days before the first menstrual bleeding until 3rd day before the 3rd menstrual bleeding (normalized to a standard 56-day period). Treatment period: 2 days before the withdrawal bleeding (WB) of the 1st evaluable treatment cycle until 3rd day before the WB of the cycle after the 2nd evaluable treatment cycle (normalized to a standard 56-day period).
Subject self-assessed pelvic pain or headache per visual analog scale (VAS) values during the menstrual/withdrawal bleeding episode and Baseline. The VAS consists of a 100 mm long straight line, with verbal anchors at either end, representing a continuum of pain intensity. Accordingly, the scale ranges from 0 mm (absence of pain) to 100 mm (unbearable pain), and the change ranges from -100 mm (best) to 100 mm (worst).
At least 6, up to 8 criteria to be met in complete response during 90-day period: no bleeding episodes(BE) \>7 days, no \>4 BE, no BE with blood loss (menstrual blood loss, MBL) ≥80 mL, no \>1 BE increase from baseline, no increase from baseline in individual patient's total number of bleeding days and total number of bleeding days not \>24 days. Additionally, for subjects included with prolonged bleeding: decrease between maximum duration during run-in and efficacy ≥2 days excessive bleeding: MBL associated with each episode decreased by ≥50% from average of qualifying episodes during run-in.
| Arm | Type | Description |
|---|---|---|
| Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027) | EXPERIMENTAL | Daily oral administration of one tablet SH T00658ID (BAY86-5027) plus one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles |
| Ethinyl estradiol, Levonorgestrel (Miranova) | ACTIVE_COMPARATOR | Daily oral administration of one tablet placebo plus one tablet SH D593B (Miranova) for 28 days without tablet-free interval for 3 treatment cycles |
| Ortho Tri-Cyclen Lo | ACTIVE_COMPARATOR | Daily oral administration of one capsule Ortho Tri-Cyclen Lo \[Ethinylestradiol (EE)/ Norgestimate (NGM)\] for 21 days, followed by one capsule placebo for 7 days (28 days total per cycle) for 13 treatment cycles (treatment encapsulated) |
| Estradiol valerate/Dienogest (Natazia, Qlaira, BAY86-5027) | EXPERIMENTAL | A blister consists of 28 tablets taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo. |
| Placebo | PLACEBO_COMPARATOR | Matching placebo to be taken orally daily. |
| Arm 1 | EXPERIMENTAL | - |
| Arm 2 | ACTIVE_COMPARATOR | - |
| Arm 3 | ACTIVE_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027) | DRUG | Daily oral administration of one tablet SH T00658ID for 28 days per cycle in the respective treatment period; no tablet-free interval |
| Ethinyl estradiol, Levonorgestrel (Miranova) | DRUG | Daily oral administration of one tablet for 28 days per cycle in the respective treatment period; no tablet-free interval |
| Placebo Match to SH T00658ID | DRUG | Daily oral administration of one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles. |
| Placebo Match to SH D593B | DRUG | Daily oral administration of one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles. |
| Ortho Tri Cyclen Lo | DRUG | Dose--Ethinylestradiol (EE) + Norgestimate (NGM) Triphasic 21-day regimen. Daily oral administration of one encapsulated Ortho Tri-Cyclen Lo for 28 days per Cycle, for 13 treatment cycles: Days 1-7, 0.025 mg EE+0.180 NGM; Days 8-14, 0.025 mg EE+0.215 NGM; Days 15-21, 0.025 mg EE+0.250 NGM; Days 27-28, placebo |
| Estradiol valerate/Dienogest (Natazia, Qlaira, BAY86-5027) | DRUG | 1 pill per day taken orally over 7 cycles of 28 pills per cycle |
| Placebo | DRUG | 1 pill per day taken orally over 7 cycles of 28 pills per cycle |
| Estradiol Valerate (EV) / Levomefolate Calcium (BAY98-7078) | DRUG | Oral, single dose, 3 mg EV + 0.451 mg levomefolate calcium, washout phase between treatments: at least 7 days |
| Estradiol Valerate (EV) (BAY86-4980) | DRUG | Oral, single dose, 3 mg EV, washout phase between treatments: at least 7 days |
| Levomefolate Calcium (BAY86-7660) | DRUG | Oral, single dose, 0.451 mg levomefolate calcium, washout phase between treatments: at least 7 days |
Inclusion Criteria: * Otherwise healthy female subjects requesting contraception and suffering from primary dysmenorrhea with a sum score for dysmenorrheic pain intensity of \>/= 8 over 2 baseline cycles documented by a prospective self-rated sum pain score * Age: 14 - 50 years (inclusive; smokers ...
Estradiol valerate/levomefolate calcium is being studied for contraception, metrorrhagia (dysfunctional uterine bleeding), and primary dysmenorrhea. It combines estradiol valerate, an estrogen, with levomefolate calcium, a folate supplement. Bayer AG is developing the combination, which is in Phase 3 development.
Estradiol valerate/levomefolate calcium targets ESR1, the estrogen receptor alpha, as an agonist. Estradiol valerate binds and activates this receptor, while levomefolate calcium provides a folate source. The ESR1 agonist activity underlies the contraceptive and gynecologic effects being studied in the program.
Bayer AG is developing estradiol valerate/levomefolate calcium. Bayer trades on the OTC market under the ticker BAYRY. The company is the sponsor of the clinical trials evaluating the combination for contraception, metrorrhagia, and primary dysmenorrhea.
Estradiol valerate/levomefolate calcium is in Phase 3 development. It is an investigational combination and has not been approved by the FDA for the indications being studied. The program includes completed Phase 3 trials in contraception, primary dysmenorrhea, and metrorrhagia, plus a completed Phase 1 bioequivalence study.
Completed trials include NCT00909857, a Phase 3 study in primary dysmenorrhea with 507 participants; NCT00754065, a Phase 3 contraception study with 409 participants; NCT00307801, a Phase 3 metrorrhagia study with 231 participants; and NCT01031355, a Phase 1 bioequivalence study with 42 participants. All four trials are completed.
Estradiol valerate/levomefolate calcium is also known as BAY98-7078. It is distinct from Natazia and Qlaira, which are estradiol valerate/dienogest combinations also developed by Bayer. The levomefolate calcium component differentiates this combination from the dienogest-containing products.