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A Placebo-Controlled, Phase 3 Study of TAK-385 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids

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ClinicalTrials.gov Identifier: NCT02655224
Recruitment Status : Completed
First Posted : January 13, 2016
Last Update Posted : June 9, 2017
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to evaluate the efficacy of TAK-385 40 mg administered orally once daily for 12 weeks, compared with placebo in participants having pain symptoms associated with uterine fibroids.

Condition or disease Intervention/treatment Phase
Uterine Fibroids Drug: TAK-385 40 mg Drug: TAK-385 placebo Phase 3

Detailed Description:

This is a phase 3, multicenter, randomized, double-blind, parallel-group study to evaluate the efficacy of TAK-385 40 mg administered orally once daily for 12 weeks compared with placebo in participants having pain symptoms associated with uterine fibroids.

Participants must be diagnosed to have uterine fibroids confirmed by transvaginal ultrasound or other methods. Participants must experience pain symptoms associated with uterine fibroids (eg, lower abdominal pain and low back pain). The total number of participants to be randomized under double-blind conditions is 64 (32 participants each for the TAK-385 40 mg group or placebo group).


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Oral TAK-385 40 mg in the Treatment of Pain Symptoms Associated With Uterine Fibroids
Actual Study Start Date : May 24, 2016
Actual Primary Completion Date : May 12, 2017
Actual Study Completion Date : May 12, 2017

Arm Intervention/treatment
Experimental: TAK-385 40 mg
TAK-385 placebo administered orally once daily before breakfast + TAK-385 40 mg administered orally once daily before breakfast
Drug: TAK-385 40 mg
TAK-385 placebo tablets + TAK-385 40 mg tablets

Placebo Comparator: TAK-385 placebo
TAK-385 placebo administered orally once daily before breakfast + TAK-385 placebo administered orally once daily before breakfast
Drug: TAK-385 placebo
TAK-385 placebo tablets + TAK-385 placebo tablets




Primary Outcome Measures :
  1. Proportion of participants with a maximum NRS score of 1 or less during the 28 days before the final dose of study drug (Week 12) [ Time Frame: Week 12 ]
    NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.


Secondary Outcome Measures :
  1. Proportion of participants with a maximum NRS score of 0 during the 28 days before the final dose of study drug (Week 12) [ Time Frame: Up to 28 days before Week 12 ]
    NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.

  2. Mean NRS score during the 28 days before the final dose of study drug (Week 12) [ Time Frame: Up to 28 days before Week 12 ]
    NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.

  3. Number of days without pain symptoms (NRS = 0) during the 28 days before the final dose of study drug [ Time Frame: Up to 28 days before Week 12 ]
    Number of days without pain symptoms is determined from zero score in NRS. NRS score is a 11-item self-reported instrument assessing pain. It includes 11 items from 0 (No Pain), 1-3 (Mild Pain), 4-6 (Moderate Pain), and 7-10 (Severe Pain). Higher scores reflect greater level of pain.

  4. Number of Participants Reporting One or More Treatment-emergent Adverse Events [ Time Frame: Up to 28 days from Week 12 ]
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  5. Number of Participants who have AEs related to Vital Signs [ Time Frame: Up to 28 days from Week 12 ]
    Vital signs included sitting blood pressure (after the participant has rested for at least 5 minutes), body temperature (oral or tympanic measurement) (degree Celsius) and pulse (bpm).

  6. Number of Participants who have AEs related to Body Weight [ Time Frame: Up to 28 days from Week 12 ]
    Number of participants with any markedly abnormal values in participant's weight collected throughout study.

  7. Number of Participants who have AEs related to Standard 12-lead Electrocardiogram (ECG) [ Time Frame: Up to 28 days from Week 12 ]
    Number of participants with any markedly abnormal values in electrocardiograms collected throughout study.

  8. Number of Participants who have AEs related to Laboratory Tests [ Time Frame: Up to 28 days from Week 12 ]
    Number of participants with any markedly abnormal values in laboratory tests collected throughout study.



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion Criteria for Entering the Screening (at VISIT 1)

    1. In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.
    2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.
    3. Prior to VISIT 1, the participant has a diagnosis of uterine fibroids confirmed by transvaginal ultrasound, abdominal ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), or laparoscopy, and has never received surgical treatment for the myoma (measurable noncalcified myoma with a longest diameter of ≥3 cm).
    4. The participant is a premenopausal Japanese woman.
    5. The participant is aged 20 years or older on the day of signing and dating the informed consent form.
    6. The participant has 1 or more measurable noncalcified myomas with a longest diameter of ≥3 cm confirmed by transvaginal ultrasound.
    7. The participant has experienced 1 or more regular menstrual cycles (25 to 38 days) immediately prior to VISIT 1 and that should include menstrual bleeding of at least 3 consecutive days.
    8. The participant who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

      Inclusion Criteria for Entering the Run-in (at VISIT 2)

    9. The participant has experienced regular menstrual cycles (25 to 38 days) immediately prior to VISIT 2 that should include menstrual bleeding of at least 3 consecutive days (at least 2 regular menstruation cycles to be confirmed by Inclusion criteria #7 and #9).

      Inclusion Criteria for Entering the Treatment (at VISIT 3)

    10. The participant has 1 or more measurable noncalcified myomas, with a longest diameter of ≥3 cm confirmed by transvaginal ultrasound (the same myoma should be measured as in Inclusion criterion #6).
    11. The participant has a maximum Numerical Rating Scale (NRS) score of ≥4 in 1 menstrual cycle just before VISIT 3.
    12. The participant has pain symptoms associated with uterine fibroids of at least 2 days in 1 menstrual cycle just before VISIT 3.
    13. The participant has experienced regular menstrual cycles (25 to 38 days) after VISIT 1 that should include menstrual bleeding of at least 3 consecutive days (at least 3 regular menstruation cycles to be confirmed by Inclusion criteria #7, #9 and #13).

Exclusion Criteria:

  1. The participant has received any investigational compound within 24 weeks prior to the start of the administration of the study medication for the day of first menstruation after VISIT 1.
  2. The participant has received TAK-385 (including placebo) in a previous clinical study.
  3. The participant is an immediate family member, study site employee, or is in a dependant relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
  4. The participant has lower abdominal pain due to irritable bowel syndrome or severe interstitial cystitis.
  5. The participant has a current history of thyroid gland disorder with irregular menstruation, or has a potential for irregular menstruation due to thyroid gland disorder, as determined by the investigator or subinvestigator.
  6. The participant has a previous or current history of pelvic inflammatory disease within the 8 weeks prior to VISIT 1.
  7. The participant has a positive Pap smear test result conducted within the 1 year prior to VISIT 1 (if there are no previous test results, those who were judged positive in the test conducted before VISIT 2).
  8. The participant has a history of panhysterectomy or bilateral oophorectomy.
  9. The participant has had markedly abnormal uterine bleeding or anovulatory bleeding, as determined by the investigator or subinvestigator.
  10. The participant has a malignant tumor or a history of a malignant tumor within the 5 years prior to VISIT 1.
  11. The participant has been treated with selective estrogen receptor modulators (SERMs) (excluding drugs for external use and dietary supplements) within the 4 weeks prior to VISIT 2.
  12. The participant has been treated with any of the following drugs within the 8 weeks prior to VISIT 2: oral contraceptive or sex hormone preparations (norethindrone, norethisterone, medroxyprogesterone, estrogen, or other progestins), and within the 16 weeks prior to VISIT 2: gonadotropin-releasing hormone (GnRH) analogues, dienogest, danazol, or aromatase inhibitors (for 1- and 3-month sustained-release preparations, within the 20 and 28 weeks prior to VISIT 2, respectively).
  13. The participant has a previous or current history of severe hypersensitivity or severe allergies to drugs.
  14. The participant has nondiagnosable abnormal genital bleeding.
  15. Female participant who is pregnant, lactating, or intending to become pregnant or to donate ova prior to signing of informed consent, during the study period, or within 1 month after the end of the study.
  16. The participant has clinically significant cardiovascular disease (eg, myocardial infarction or unstable angina pectoris within the 24 weeks prior to VISIT 1) or uncontrollable hypertension (eg, resting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at Screening and Run-in).
  17. The participant is inappropriate for participation in this study based on standard 12-lead electrocardiogram (ECG) findings, as determined by the investigator or subinvestigator.
  18. The participant has active liver disease or jaundice, or with alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin (total bilirubin) >1.5 times the upper limit of normal (ULN) in the clinical laboratory tests at VISIT 1 and 2.
  19. The participant has previous or current history of diseases considered to be inappropriate for participation in this study, including severe hepatic impairment, jaundice, renal impairment, cardiovascular disease, endocrine system disease, metabolic disorder, pulmonary disease, gastrointestinal disease, neural disease, urological disease, immune disease, or mental disorder (especially depression-like symptoms) or suicide attempt resulting from a mental disorder.
  20. The participant has a previous or current history of drug abuse (defined as any illicit drug use) or alcohol abuse.
  21. The participant is inappropriate for participation in this study for other reasons, as determined by the investigator or subinvestigator.

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): NCT02655224


Locations
Japan
Matsudo, Chiba, Japan
Ebetsu, Hokkaido, Japan
Sapporo, Hokkaido, Japan
Nishinomiya, Hyogo, Japan
Ibaraki, Osaka, Japan
Sakai, Osaka, Japan
Bunkyo-ku, Tokyo, Japan
Minato-ku, Tokyo, Japan
Setagaya-ku, Tokyo, Japan
Kagoshima, Japan
Osaka, Japan
Sponsors and Collaborators
Takeda
Investigators
Study Director: Medical Director Takeda

Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02655224     History of Changes
Other Study ID Numbers: TAK-385-3008
U1111-1178-1086 ( Registry Identifier: WHO )
First Posted: January 13, 2016    Key Record Dates
Last Update Posted: June 9, 2017
Last Verified: June 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leiomyoma
Myofibroma
Pain
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Connective Tissue Diseases
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms