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Bay1002670, Fibroids, Safety and Efficacy EU,US,Can, Jap (ASTEROID 1)

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ClinicalTrials.gov Identifier: NCT02131662
Recruitment Status : Completed
First Posted : May 6, 2014
Results First Posted : December 8, 2017
Last Update Posted : December 8, 2017
Sponsor:
Information provided by (Responsible Party):
Bayer

Brief Summary:
The study is performed to assess the efficacy and safety of different doses of BAY1002670 in subjects with uterine fibroids. The dose-response relationship will be evaluated. Further, the study aims to establish a population pharmacokinetic/pharmacodynamic relationship for BAY1002670 in subjects with uterine fibroids. To assess the efficacy of BAY1002670 the interchangeability of menstrual pictogram and alkaline hematin method for the judgement of menstrual blood loss will be assessed.

Condition or disease Intervention/treatment Phase
Leiomyoma Drug: BAY1002670 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 309 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Parallel-group, Double-blind, Placebo Controlled, Multi-center Study to Assess the Efficacy and Safety of Different Doses of BAY1002670 in Subjects With Uterine Fibroids Over 3 Months
Actual Study Start Date : May 15, 2014
Actual Primary Completion Date : May 4, 2016
Actual Study Completion Date : May 4, 2016

Arm Intervention/treatment
Experimental: VPR 4 mg Drug: BAY1002670
Subjects received 4 milligram (mg) Vilaprisan (VPR) tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.

Experimental: VPR 2 mg Drug: BAY1002670
Subjects received 2 mg VPR tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.

Experimental: VPR 1 mg Drug: BAY1002670
Subjects received 1 mg VPR tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.

Experimental: VPR 0.5 mg Drug: BAY1002670
Subjects received 0.5 mg VPR tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.

Placebo Comparator: Placebo Drug: Placebo
Subjects received matching placebo tablet once daily orally for 12 weeks (84 days) from the first week of the menstrual cycle following randomization.




Primary Outcome Measures :
  1. Percentage of Subjects With Amenorrhea, Defined as no Scheduled or Unscheduled Bleeding/Spotting After the End of the Initial Bleeding Episode Until End of Treatment [ Time Frame: After end of the initial bleeding episode until the end of treatment, up to 12 weeks ]
    Amenorrhea was defined as no scheduled or unscheduled bleeding/spotting after the end of the initial bleeding episode until end of treatment. Dose-response curve was estimated based on the primary endpoint. The 4 parameters characterizing the dose-response curve were reported in other pre-specified endpoints below.


Secondary Outcome Measures :
  1. Change in Volume of Menstrual Blood Loss Per 28 Days From Baseline During Treatment by Reference Period (Assessed by Alkaline Hematin Method) [ Time Frame: From baseline to end of follow-up ]
    In the below table, "N" signifies subjects who were evaluable for the specific parameter at that timepoint for each arm, respectively.

  2. Time to Onset of Controlled Bleeding [ Time Frame: During treatment period ]
    Onset of controlled bleeding was defined by the first day, for which the MBL (assessed by MP, Version 2014) for all subsequent 28-day periods up to the end of the treatment period was less than 80 mL. Kaplan-Meier estimated time to onset of controlled bleeding (days) was reported.

  3. Change in Volume of Largest Fibroid Compared to Baseline Measured by MRI [ Time Frame: From baseline to end of follow-up period ]
    Pelvic Magnetic resonance imagings (MRI), without contrast agents, were performed for volume measurements of the uterus and fibroids preferably using 1.5 Tesla scanners or higher. Images were sent to the imaging core laboratory for evaluation. Volume measurements of the uterus and fibroids were performed centrally by independent radiologist(s).


Other Outcome Measures:
  1. Exposure-response Analysis of Vilaprisan - Percentage of Subjects Achieving Maximum Effect (Emax) of Induced Amenorrhea [ Time Frame: From start of the study treatment to Day 84 (treatment period) ]
    Maximum effect of vilaprisan on induced amenorrhea during treatment period. Induced amenorrhea was defined as number of subjects with amenorrhea (that is, all days with bleeding intensity 1 = none) , i.e. no bleeding or spotting allowed after initial bleeding episode until end of treatment. The nature of this exposure response analysis was the development of a model valid for the exposure response relationship over the entire range of available exposures (i.e. across all dose groups). Therefore, observations (exposure - induced amenorrhea) of all subjects need to be combined.

  2. Steady-state Exposure Achieving Half-maximal Effect (EAUC50) of Induced Amenorrhea During Treatment Period of Vilaprisan [ Time Frame: From start of the study treatment to Day 84 (treatment period) ]
    Area-under-the-curve (AUC) of vilaprisan between 0 and 24 hours post-dose at steady-state achieving 50% of maximum effect of vilaprisan on induced amenorrhea during treatment period. Induced amenorrhea was defined as number of subjects with induced-amenorrhea (that is, all days with bleeding intensity 1 = none) , i.e. no bleeding or spotting allowed after initial bleeding episode until end of treatment. The nature of this exposure response analysis was the development of a model valid for the exposure response relationship over the entire range of available exposures (i.e. across all dose groups). Therefore, observations (exposure - induced amenorrhea) of all subjects need to be combined.

  3. Exposure-response Analysis of Vilaprisan - Predicted Percentage of Subjects Below 90% of the Maximum Probability of Induced Amenorrhea [ Time Frame: From start of the study treatment to Day 84 (treatment period) ]
    The final exposure-response model was used to simulate the percentage of subjects below 90% of the maximum probability of induced amenorrhea (that is, all days with bleeding intensity 1 = none) for the selected doses 1, 2 and 3 mg (see table below).

  4. Assessment of MP to Identify Subjects With Heavy Menstrual Bleeding (HMB) [ Time Frame: At baseline ]
    The ability of the MP to identify subjects with HMB (defined as > 80 mL of blood loss during bleeding episode) per 28 days against the the current gold standard (i.e. AH method) was assessed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MP method for detecting heavy menstrual bleeding were calculated against AH method. Sensitivity = true positive/(true positive + false negative)*100; Specificity = true negative/(true negative + false positive)*100; PPV = true positive/(true positive + false positive)*100; NPV = true negative/(true negative + false negative)*100. MP version 2014 was originally defined based on studies in healthy subjects. And MP version 2016 was developed for study population of women with heavy bleeding.

  5. Percentage of Subjects With Amenorrhea (Defined as MBL < 2 mL) During the Last 28 Days of Treatment [ Time Frame: Last 28 Days of Treatment ]
  6. Percentage of Subjects With HMB Response During the Last 28 Days of Treatment [ Time Frame: Last 28 Days of Treatment ]
  7. Estimated Dose-response Curve Based on Amenorrhea - E0 and Emax [ Time Frame: After end of the initial bleeding episode until the end of treatment ]
    The primary objective was to estimate the dose-response curve based on the primary endpoint: subjects with amenorrhea. The number of subjects with amenorrhea was assumed to be binomial distributed. A 4 parameters logistic model was used to fit the observed data for characterizing the dose-response curve: E0, Emax, ED50 and δ. The model is defined as p(d)=E0 + Emax/{1+ e^[{ED50-d)/δ]}. E0 is the amenorrhea rate for placebo; Emax is the maximum effect attributable to the drug (compared with the basal effect with dose at d=0 [placebo group], the maximum increase of drug effect).

  8. Estimated Dose-response Curve Based on Amenorrhea - ED50 [ Time Frame: After end of the initial bleeding episode until the end of treatment ]
    The primary objective was to estimate the dose-response curve based on the primary endpoint: subjects with amenorrhea. The number of subjects with amenorrhea was assumed to be binomial distributed. A 4 parameters logistic model was used to fit the observed data for characterizing the dose-response curve: E0, Emax, ED50 and δ. The model is defined as p(d)=E0 + Emax/{1+ e^[{ED50-d)/δ]}. ED50 is the dose at which 50% of Emax were achieved.

  9. Estimated Dose-response Curve Based on Amenorrhea - δ [ Time Frame: After end of the initial bleeding episode until the end of treatment ]
    The primary objective was to estimate the dose-response curve based on the primary endpoint: subjects with amenorrhea. The number of subjects with amenorrhea was assumed to be binomial distributed. A 4 parameters logistic model was used to fit the observed data for characterizing the dose-response curve: E0, Emax, ED50 and δ. The model is defined as p(d)=E0 + Emax/{1+ e^[{ED50-d)/δ]}. δ is hill slope parameter which measures sensitivity of the response to the dose range of the drug, determining the steepness of the dose-response curve.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated informed consent
  • Diagnosis of uterine fibroid(s) documented by transvaginal or abdominal ultrasound at screening with at least 1 fibroid with largest diameter 3.0 cm
  • 18 to 50 years of age at the time of screening
  • Heavy menstrual bleeding >80 mL documented by MP during the bleeding episode following the screening visit
  • Normal or clinically insignificant cervical smear not requiring further follow-up
  • An endometrial biopsy performed at the screening visit 1 (Visit 1), without significant histological disorder such as endometrial hyperplasia or other significant endometrial pathology
  • Use of a non-hormonal barrier method of contraception starting at the bleeding episode following the screening visit 1 (Visit 1) until the end of the study
  • Good general health (except for findings related to uterine fibroids)

Exclusion Criteria:

  • Pregnancy or lactation
  • Uterine fibroid with largest diameter >10.0 cm
  • Hypersensitivity to any ingredient of the study drug
  • Laboratory values outside inclusion range before randomization and considered as clinically relevant
  • Hemoglobin values <6 g/dL or any condition requiring immediate blood transfusion (subjects with hemoglobin values <10.9 g/dL will receive iron supplementation)
  • Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02131662


  Show 105 Study Locations
Sponsors and Collaborators
Bayer
Investigators
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Study Director: Bayer Study Director Bayer

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02131662     History of Changes
Other Study ID Numbers: 15788
2013-003945-40 ( EudraCT Number )
First Posted: May 6, 2014    Key Record Dates
Results First Posted: December 8, 2017
Last Update Posted: December 8, 2017
Last Verified: November 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Uterine fibroids
Additional relevant MeSH terms:
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Leiomyoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms