Clinical trial NCT01588236: Effect of KYG0395 on Primary Dysmenorrhea
Official title: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Phase 2 Study to Further Assess the Efficacy, Safety and Dose Response of KYG0395 in the Treatment of Primary Dysmenorrhea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Dysmenorrhea
Lead sponsor: Jiangsu Kanion Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2012-04-30
Enrollment: 280
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to further assess the efficacy, safety and dose-response of KYG0395 in the treatment of primary dysmenorrhea.

Detailed description: Compare the effect and safety of the investigational drug and placebo on dysmenorrhea in adult otherwise healthy women.

Eligibility criteria: Inclusion Criteria:

1. Reviewed and signed the ICF.
2. Female between the ages of 18 and 35 (inclusive) at the time of signing the ICF.
3. Otherwise healthy female subjects with primary dysmenorrhea for at least 3 consecutive menstrual cycles prior to the study (prior to the start of the baseline cycles) and with VAS score \>70 for the maximum dysmenorrheic pain or VAS score \>40 for the average daily dysmenorrheic pain of the last menstrual cycle.
4. Recent (last 6 months) history of regular menstrual cycles. Regular menstrual cycle meant the period of the cycle fell in the range of 21 to 35 days.
5. No contraceptive injection, implant, or intrauterine device within 6 months prior to the study and willing not to use any of them during the entire study period. Subject agreed to the use of a highly effective method of contraception throughout the study including:

   * 28-day regimens of combined oral contraceptives, patches, or rings
   * Bilateral tubal sterilization
   * Partner vasectomy
   * Condoms and spermicide
   * Diaphragm and spermicide At the discretion of the investigator, total abstinence was permitted as a method where age, lifestyle, or sexual orientation of the subject ensured compliance. If the subject was taking combined hormonal contraception, it had to be taken for at least 6 months prior to screening and be used throughout the duration of the study without interruption. No more than 50% of enrolled subjects were to be taking combined hormonal contraception.
6. Agreed not to use any dietary supplement or alternative medication intended to treat dysmenorrhea and/or its accompanying symptoms during the entire study period.
7. Was able to tolerate ibuprofen and willing to use only ibuprofen supplied by the sponsor for this study as a rescue medication.
8. Was able to understand and follow the study instructions, to complete the electronic subject diary, and to communicate with the investigator and staff.

Exclusion Criteria:

1. Known or suspected to have secondary dysmenorrhea due to pelvic inflammation, endometriosis, uterine myomata, ovarian pathological changes, or other pelvic diseases.
2. Known or suspected to have gastrointestinal or urological conditions that may cause abdominal/pelvic pain, such as colitis, appendicitis, irritable bowel syndrome, cholelithiasis, interstitial cystitis, urocystitis, nephrolithiasis, and other conditions that, according to the investigator's judgment, are not suitable for the study.
3. Use of an intrauterine contraceptive device, contraception injection, contraceptive implant, progesterone-only contraceptive pills, or an extended-cycle combined hormonal contraceptive regimen that does not foster cyclic withdrawal bleeding every 28 days within 6 months of screening or during the study.
4. Screening pelvic ultrasound findings suggestive of significant pathology including secondary causes of dysmenorrhea such as more than 2 uterine fibroids \>3 cm in diameter, or complex ovarian cysts. At the discretion of the investigator, simple ovarian cysts \<3 cm in diameter or functional ovarian cysts that were deemed to not require follow-up were permitted.
5. Obesity: body mass index (BMI) \>32 kg/m2.
6. Positive gonorrhea and/or chlamydia test or evidence of other active sexually transmitted disease that, in the investigator's opinion, would make the subject not suitable for the study.
7. Known allergy to the study drug, or hypersensitivity to any of the study drug ingredients, or known allergy or intolerance to one or more of the excipients: β cyclodextrin and lactose, and according to the investigator's judgment, the allergy/intolerance was so severe that the subject was not suitable for the study.
8. Presence of one or more than one of the following: cerebrovascular disease, cardiovascular disease, pulmonary embolism, coagulopathy, thrombophlebitis, optic neuritis, retinal vein thrombosis, liver tumor, kidney tumor, renal failure, hepatitis, or other serious primary diseases of hepatic, renal or hematopoietic systems and mental disorders that according to the investigator's judgment renders the subject unsuitable for the study; or any chronic disease(s) for which the subject had been taking long term medication, and according to the investigator's judgment was unsuitable for the study. The investigator may have contacted the medical monitor and/or sponsor with questions about whether a subject was suitable for the study.
9. Hypertension, defined as sitting blood pressure (BP) systolic \>140 mm Hg or diastolic \>90 mm Hg (repetition of the measurement of BP was permitted to confirm the subject's hypertension condition).
10. Pregnant or trying to conceive during the study. Recent delivery, abortion, or lactation within 3 menstrual cycles before the start of treatment.
11. Alcoholism or drug abuse within the last 6 months prior to the study.
12. Regular use of any concomitant medications that might have confounded efficacy and/or safety assessments including, but not limited to, the following: narcotic, non NSAID, or NSAID analgesics for the treatment of conditions other than dysmenorrhea, psychotropic drugs, antidepressants, sedative hypnotics, sedating antihistamines, muscle relaxants, or tranquilizers. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors were permitted for indications other than pain provided that the subject had been on a stable dose for at least 2 menstrual cycles before providing consent for this study and agreed to remain on a stable dose throughout the course of the study.
13. Simultaneous participation in another clinical study or use of any experimental drug or device, or being a subject in another clinical research program within 30 days prior to the screening visit.
14. Use of any dietary supplement or alternative medication intended to treat dysmenorrhea or its accompanying symptoms within 30 days prior to the screening visit.
15. Major surgery scheduled for the study period.
16. Known to have a positive human immunodeficiency virus test.
17. Abnormal Papanicolaou (PAP) test results, except atypical squamous cells of unknown significance with reflex human papillomavirus test negative.
18. Inability to follow study procedures for any reason, including the following examples: language comprehension, psychiatric illness, or inability to get to the study center.
19. Had a clinically significant deviation from normal in any of the screening tests or examinations.
20. Had the presence of all 3 of the following signs and symptoms during the 2 weeks prior to screening.

    * Reported that her usual urine color was grade 7 or above on the pictorial scale (provided in the GF-2011-001 Special Assessment Guide) and laboratory examination of the color of her urine at screening confirmed this
    * Reported that she usually had dry stools and had experienced constipation for at least 2 consecutive days
    * Was noted on the screening examination by the investigator to have a red tongue with a yellow coating (example photograph provided in the GF 2011 001 Special Assessment Guide)

Primary outcomes:
measure: The Change From Baseline to the End of Treatment Period in Maximum Dysmenorrheic Pain VAS Score
timeFrame: Baseline and end of treatment (6 months)
measure: The Change From Baseline in Number of Days With Dysmenorrheic Pain at the End of Treatment
timeFrame: Baseline and end of treatment (6 months)
measure: The Change From Baseline to the End of Follow-up Period in the Maximum VAS Score
timeFrame: Baseline and end of follow-up (9 months)
measure: The Number of Days of Dysmenorrheic Pain at the End of Follow-up Period Compared With Baseline
timeFrame: Baseline and end of follow-up (9 months)
Secondary outcomes:
measure: Average Daily Dysmenorrheic Pain VAS Score at the End of Treatment and Follow-up Period
timeFrame: Baseline, end of treatment (6 months) and end of follow-up (9 months)
measure: Rescue Medication Consumption at the End of Treatment and Follow-up Period
timeFrame: Baseline, end of treatment (6 months) and end of follow-up (9 months)
measure: Subject's Overall Satisfaction at the End of the 3-cycle Follow-up Period
timeFrame: Base line and end of follow-up (9 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Women's Health Research
state: Arizona
city: Little Rock
country: United States
facility: Lynn Institute of the Ozarks
state: Arkansas
city: San Diego
country: United States
facility: Women's Health Care at Frost Street
state: California
city: New London
country: United States
facility: Coastal Connecticut Research
state: Connecticut
city: Atlanta
country: United States
facility: Atlanta Women's Research Institute, Inc.
state: Georgia
city: Idaho Falls
country: United States
facility: Women's Healthcare Associates dba Rosemark WomenCare Specialists
state: Idaho
city: Chicago
country: United States
facility: Chicago Research Center, Inc.
state: Illinois
city: Fall River
country: United States
facility: Genesis Clinical Research
state: Massachusetts
city: Ann Arbor
country: United States
facility: ClinSite
state: Michigan
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: Lawrenceville
country: United States
facility: Lawrence OB GYN Associates
state: New Jersey
city: Plainsboro
country: United States
facility: The Center for Women's Health and Wellness LLC
state: New Jersey
city: Port Jefferson
country: United States
facility: Suffolk OB-GYN
state: New York
city: Winston-Salem
country: United States
facility: Lynhurst Clinical Research
state: North Carolina
city: Columbus
country: United States
facility: Columbus Center for Women's Health Research
state: Ohio
city: Pittsburgh
country: United States
facility: Clinical Trials Research Services
state: Pennsylvania
city: Columbia
country: United States
facility: SC Clinical Research Center, LLC
state: South Carolina
city: Nashville
country: United States
facility: Dial Research Associates, Inc.
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Corpus Christi
country: United States
facility: Advanced Research Associates
state: Texas
city: Houston
country: United States
facility: Advances in Health
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: Seattle
country: United States
facility: Women's Clinical Research Center
state: Washington
Study officials:
affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd
name: Xiaoming Song, MD
role: STUDY_DIRECTOR
References: