SH T00186 Phase II/ III Optimal Drospirenone (DRSP) Dose Finding and Placebo-controlled Comparative Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00511797
First received: August 3, 2007
Last updated: December 25, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to investigate efficacy of drospirenone for dysmenorrhea.


Condition Intervention Phase
Dysmenorrhea
Drug: SH T04740B
Drug: SH T00186DF
Drug: SH T04740F
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Comparative Study to Investigate the Optimal Dose of Drospirenone for Dysmenorrhea With SH T04740A [Drospirenone 1 mg/Ethinylestradiol 20 µg (as ß-cyclodextrin Clathrate)], SH T 04740E [Drospirenone 2 mg/Ethinylestradiol 20 µg (as ß-cyclodextrin Clathrate)] and SH T00186D [Drospirenone 3 mg/ Ethinylestradiol 20 µg (as ß-cyclodextrin Clathrate)] Administered Orally for 16 Weeks (4 Cycles), and to Confirm the Efficacy of SH T00186D for Dysmenorrhea.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Change From Baseline in Total Dysmenorrheal Score at Final Evaluation [ Time Frame: Baseline and up to 4 Cycles (28 days per cycle) ] [ Designated as safety issue: No ]
    Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)


Secondary Outcome Measures:
  • Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 [ Time Frame: Baseline and up to 4 Cycles (28 days per cycle) ] [ Designated as safety issue: No ]
    Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6.

  • Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Severity of lower abdominal pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).

  • Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Severity of low back pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).

  • Number of Participants With Severity of Headache During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Severity of headache during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).

  • Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Severity of nausea or vomiting during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).

  • Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.

  • Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 [ Time Frame: From baseline up to Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).

  • Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 [ Time Frame: Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).

  • Change From Baseline in Endometrial Thickness After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Endometrial thickness was measured via transvaginal ultrasound examination. The endometrium is the inner membrane of the uterus. During the menstrual cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue layer.

  • Number of Bleeding / Spotting Episodes [ Time Frame: For the first 90 days ] [ Designated as safety issue: No ]
    Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. An episode means a series of bleeding and/or spotting. The bleeding /spotting analyses are by intensity.

  • Number of Bleeding / Spotting Days [ Time Frame: For the first 90 days ] [ Designated as safety issue: No ]
    Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. The bleeding /spotting analyses are by intensity.

  • Participants With Withdrawal Bleeding [ Time Frame: At Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.

  • Participants With Intracyclic Bleeding [ Time Frame: At Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Intracyclic bleedings were defined as bleedings while a participant takes active drugs.

  • Participants With Non-heavy Intracyclic Bleeding [ Time Frame: At Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding).

  • Participants With Non-heavy Withdrawal Bleeding [ Time Frame: At Cycle 4 (28 dyas per cycle) ] [ Designated as safety issue: No ]
    Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding).

  • Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.

  • Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    CRP is a laboratory parameter giving an indication of inflammation, whose elevated levels that were defined by a lab suggest a potential inflammation.

  • Change From Baseline in Serum Estradiol Level After 4-cycle Treatment [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Estradiol is a predominant sex hormone that presents in female.

  • Change From Baseline in Serum Progesterone Level at Cycle 4 [ Time Frame: From baseline to Cycle 4 (28 days per cycle) ] [ Designated as safety issue: No ]
    Progesterone is a steroid hormone involving in the female menstrual cycle, pregnancy, etc.


Enrollment: 249
Study Start Date: July 2007
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DRSP 1 mg/EE 20 μg
1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Drug: SH T04740B
Drospirenone 1mg/EE 20µg (ß-CDC)
Experimental: DRSP 2 mg/EE 20 μg
1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Drug: SH T04740F
Drospirenone 2 mg/EE 20µg (ß-CDC)
Experimental: DRSP 3 mg/EE 20 μg
1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle
Drug: SH T00186DF
Drospirenone 3 mg/EE 20µg (ß-CDC)
Placebo Comparator: Placebo
1 tablet per day placebo for 28 days in each 28-day cycle
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 20 years or older at obtaining informed consent
  • Patients having the normal menstrual cycle (28+/-3 days) in the latest two menses before the final enrollment
  • Patients having a total dysmenorrhea score of at least 3 points in two menstrual cycles before the final enrollment

Exclusion Criteria:

  • Patients with ovarian chocolate cysts and symptomatic uterine fibroids (as defined in greater detail in the study protocol)
  • Patients with estrogen-dependent tumors (e.g. breast cancer, cancer of the uterine body or breast fibrocystic, etc.), and patients with cervical cancer or suspected cervical cancer (e.g. class III or greater in the cervical smear or endometrial smear examination.)
  • Patients with undiagnosed abnormal vaginal bleeding
  • Patients with thrombophlebitis, pulmonary embolism, cerebrovascular disease(including transient ischemic attack, etc.), or coronary artery disease(e.g. myocardial infarction and angina pectoris, etc.), or a history of those diseases
  • Patients aged 35 years or older who smoke at least 15 cigarettes per day
  • Patients with migraine accompanied by prodrome (e.g. scintillating scotoma or star-shaped scintillation)
  • Patients with pulmonary hypertension or valvular heart disease complicated by atrial fibrillation, and patients with a history of subacute bacterial endocarditis
  • Patients who are regularly taking nutritional products that contain St. John's Wort
  • Patients who underwent surgical treatment for endometriosis by laparotomy, or laparoscopy within 2 months prior to screening
  • Patients who need to use analgesics regularly for therapeutic objectives other than relief from the pain of dysmenorrhea during this study (occasional use permitted)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00511797

Locations
Japan
Maebashi, Gunma, Japan, 371-0024
Kobe, Hyogo, Japan, 650-0021
Nishinomiya, Hyogo, Japan, 663-8204
Yokohama, Kanagawa, Japan, 231-0861
Sendai, Miyagi, Japan, 981-0933
Chuo-ku, Tokyo, Japan, 104-0061
Hachioji, Tokyo, Japan, 192-0046
Setagaya-ku, Tokyo, Japan, 157-0066
Setagaya-ku, Tokyo, Japan, 156-0042
Toshima-ku, Tokyo, Japan, 171-0021
Kyoto, Japan, 612-0064
Osaka, Japan, 530-0013
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00511797     History of Changes
Other Study ID Numbers: 91615, 310283
Study First Received: August 3, 2007
Results First Received: April 15, 2010
Last Updated: December 25, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Bayer:
Dysmenorrhea
Dysmenorrheal score
Drospirenone
DRSP
Ethinylestradiol

Additional relevant MeSH terms:
Dysmenorrhea
Menstruation Disturbances
Pathologic Processes
Pelvic Pain
Pain
Signs and Symptoms
Ethinyl Estradiol
Drospirenone
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Diuretics, Potassium Sparing
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014