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Estradiol Valerate/ Levomefolate Calcium

Phase 3

Contraception | Small molecule | Endocrine |Bayer AG|Last Updated: Nov 20, 2024

Target and mechanism

ModalitySmall molecule

Also known as Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027), Estradiol valerate, Dienogest

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLED
Total Trials2
Total Enrollment451

FDA Designations

No designations recorded

Clinical trial landscape

Estradiol Valerate/ Levomefolate Calcium · 5 trials · 4 indications

Phase 3 4Phase 1 1
NCT00909857Effect on Primary DysmenorrheaPrimary Dysmenorrhea
COMPLETED507 Analytics
NCT00754065To Compare SH T00658ID Over Ortho Tri-Cyclen Lo (US/Canada)Contraception
COMPLETED409 Analytics
NCT00307801Efficacy and Safety Study for the Treatment of Dysfunctional Uterine BleedingMetrorrhagia
COMPLETED231 Analytics
NCT00293059Efficacy and Safety Study for the Treatment of Dysfunctional Uterine BleedingMetrorrhagia
COMPLETED190 Analytics
PHASE3COMPLETED
Effect on Primary Dysmenorrhea
Primary DysmenorrheaUnlock trial analytics
PHASE3COMPLETED
To Compare SH T00658ID Over Ortho Tri-Cyclen Lo (US/Canada)
ContraceptionUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding
MetrorrhagiaUnlock trial analytics
PHASE3COMPLETED
Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding
MetrorrhagiaUnlock trial analytics

Study Endpoints

Primary Endpoints

Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Number of Days With Dysmenorrheic Pain
baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)

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).

The Change in Average of the 3 Highest Visual Analog Scale (VAS) Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 From Baseline to Cycle 6
Day 22-28 from Baseline to Day 22-28 from Cycle 6 (28 days per Cycle)

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).

Proportion of Participants With no Dysfunctional Uterine Bleeding (DUB) Symptoms
Efficacy phase was defined as a 90-day period under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7

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.

Uncorrected Cmax and AUC(0-tlast) and baseline corrected Cmax and AUC (if possible) for E1, E2, E1S, and L-5- methyl-THF
2 months

Secondary Endpoints

Change Between Baseline Evaluation Period and Treatment Evaluation Period in the Sum of Score Points of Dysmenorrheic Pain
baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain Independent of Occurrence of Vaginal Bleeding
baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
Change Between Baseline Evaluation Period and Treatment Evaluation Period in Number of Days With Pelvic Pain During Unscheduled Bleeding
baseline period (2 baseline cycles, usually 56 days) vs. treatment period (on-treatment cycles 2 and 3, usually 56 days)
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)EXPERIMENTALDaily 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_COMPARATORDaily 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 LoACTIVE_COMPARATORDaily 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)EXPERIMENTALA 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.
PlaceboPLACEBO_COMPARATORMatching placebo to be taken orally daily.
Arm 1EXPERIMENTAL -
Arm 2ACTIVE_COMPARATOR -
Arm 3ACTIVE_COMPARATOR -

Interventions

NameTypeDescription
Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)DRUGDaily 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)DRUGDaily oral administration of one tablet for 28 days per cycle in the respective treatment period; no tablet-free interval
Placebo Match to SH T00658IDDRUGDaily oral administration of one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.
Placebo Match to SH D593BDRUGDaily oral administration of one tablet placebo for 28 days without tablet-free interval for 3 treatment cycles.
Ortho Tri Cyclen LoDRUGDose--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)DRUG1 pill per day taken orally over 7 cycles of 28 pills per cycle
PlaceboDRUG1 pill per day taken orally over 7 cycles of 28 pills per cycle
Estradiol Valerate (EV) / Levomefolate Calcium (BAY98-7078)DRUGOral, single dose, 3 mg EV + 0.451 mg levomefolate calcium, washout phase between treatments: at least 7 days
Estradiol Valerate (EV) (BAY86-4980)DRUGOral, single dose, 3 mg EV, washout phase between treatments: at least 7 days
Levomefolate Calcium (BAY86-7660)DRUGOral, single dose, 0.451 mg levomefolate calcium, washout phase between treatments: at least 7 days
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Eligibility Criteria

Age Range14 Years to 50 Years
SexFEMALE
Healthy VolunteersYes
Study Sites41

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 ...

Countries:United StatesCanadaChileGermanyItalyPhilippinesAustraliaCzechiaFinlandHungaryNetherlandsPolandSwedenUkraineUnited Kingdom
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