Effect of KYG0395 on Primary Dysmenorrhea

Phase 2

Completed

• Conditions: Primary Dysmenorrhea
• Interventions: Drug: high dose KYG0395; Drug: lower dose KYG0395; Drug: Placebo

• Registration Number: NCT01588236
• Lead Sponsor: Jiangsu Kanion Pharmaceutical Co., Ltd

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.

Study Timeline

• Study First Submitted: 2012-04-26
• Study First Submitted QC: 2012-04-27
• Study First Posted: 2012-04-30
• Study Start: 2012-05
• Primary Completion: 2015-07
• Study Completion: 2015-07
• Status Verified: 2017-04
• Results First Submitted: 2017-04-18
• Results First Submitted QC: 2019-03-01
• Last Update Submitted: 2019-03-01
• Results First Posted: 2019-03-26
• Last Update Posted: 2019-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 280

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
high dose KYG0395	high dose KYG0395	Patients received high dose KYG0395 capsule (tid)
lower dose KYG0395	lower dose KYG0395	Patients received lower dose KYG0395 capsule (bid)
placebo	Placebo	Patients received placebo (tid)

Primary Outcome Measures

Name	Time	Method
The Change From Baseline to the End of Treatment Period in Maximum Dysmenorrheic Pain VAS Score	Baseline and end of treatment (6 months)	VAS is represented by a straight line with extreme limits: from "no pain" and an associated image of a happy face at the left endpoint to "unbearable pain" and an associated image of an unhappy face at the right endpoint. The left endpoint is the minimum pain score of zero while the right endpoint is the maximum pain score of 100.; The dysmenorrheic pain (lower abdominal cramping pain) that usually occurs just before and/or during menstruation was measured in this study using a The Visual Analogue Scale (VAS). Pain was assessed during 9 menstrual cycles from the beginning of the screening to the end of follow-up.
The Change From Baseline in Number of Days With Dysmenorrheic Pain at the End of Treatment	Baseline and end of treatment (6 months)	The change from baseline in number of days with dysmenorrheic pain at the end of 3 treatment cycles
The Change From Baseline to the End of Follow-up Period in the Maximum VAS Score	Baseline and end of follow-up (9 months)	VAS is represented by a straight line with extreme limits: from "no pain" and an associated image of a happy face at the left endpoint to "unbearable pain" and an associated image of an unhappy face at the right endpoint. The left endpoint is the minimum pain score of zero while the right endpoint is the maximum pain score of 100.; The dysmenorrheic pain (lower abdominal cramping pain) that usually occurs just before and/or during menstruation was measured in this study using a The Visual Analogue Scale (VAS). Pain was assessed during 9 menstrual cycles from the beginning of the screening to the end of follow-up.
The Number of Days of Dysmenorrheic Pain at the End of Follow-up Period Compared With Baseline	Baseline and end of follow-up (9 months)	The change from baseline in the number of days with dysmenorrheic pain at the end of a 3-cycle follow-up period

Secondary Outcome Measures

Name	Time	Method
Rescue Medication Consumption at the End of Treatment and Follow-up Period	Baseline, end of treatment (6 months) and end of follow-up (9 months)	The change from baseline to the end of treatment and follow-up period in rescue medication consumption
Subject's Overall Satisfaction at the End of the 3-cycle Follow-up Period	Base line and end of follow-up (9 months)	The subject's evaluation of overall satisfaction was recorded in the electronic subject diary at the end of the 3 treatment cycles and at the end of the 3-cycle follow-up period (at the end of the day before the subject goes to bed) using the numeric rating scale provided below: 0=None, Not satisfied with the treatment outcome； 1. Mild, Mildly satisfied with the treatment outcome； 2. Most, Mostly satisfied with the treatment outcome； 3. Complete, Completely satisfied with the treatment outcome.
Average Daily Dysmenorrheic Pain VAS Score at the End of Treatment and Follow-up Period	Baseline, end of treatment (6 months) and end of follow-up (9 months)	VAS is represented by a straight line with extreme limits: from "no pain" and an associated image of a happy face at the left endpoint to "unbearable pain" and an associated image of an unhappy face at the right endpoint. The left endpoint is the minimum pain score of zero while the right endpoint is the maximum pain score of 100.; The dysmenorrheic pain (lower abdominal cramping pain) that usually occurs just before and/or during menstruation was measured in this study using a The Visual Analogue Scale (VAS). Pain was assessed during 9 menstrual cycles from the beginning of the screening to the end of follow-up.

Trial Locations

Locations (23)

Coastal Connecticut Research; 🇺🇸 New London, Connecticut, United States

Benchmark Research; 🇺🇸 Austin, Texas, United States

Columbus Center for Women's Health Research; 🇺🇸 Columbus, Ohio, United States

The Center for Women's Health and Wellness LLC; 🇺🇸 Plainsboro, New Jersey, United States

Atlanta Women's Research Institute, Inc.; 🇺🇸 Atlanta, Georgia, United States

Genesis Clinical Research; 🇺🇸 Fall River, Massachusetts, United States

Montana Medical Research; 🇺🇸 Missoula, Montana, United States

Clinical Trials Research Services; 🇺🇸 Pittsburgh, Pennsylvania, United States

SC Clinical Research Center, LLC; 🇺🇸 Columbia, South Carolina, United States

Advanced Research Associates; 🇺🇸 Corpus Christi, Texas, United States

Advances in Health; 🇺🇸 Houston, Texas, United States

Women's Clinical Research Center; 🇺🇸 Seattle, Washington, United States

Women's Health Research; 🇺🇸 Phoenix, Arizona, United States

Clinical Trials of Texas, Inc.; 🇺🇸 San Antonio, Texas, United States

Lynn Institute of the Ozarks; 🇺🇸 Little Rock, Arkansas, United States

Women's Health Care at Frost Street; 🇺🇸 San Diego, California, United States

Chicago Research Center, Inc.; 🇺🇸 Chicago, Illinois, United States

Lawrence OB GYN Associates; 🇺🇸 Lawrenceville, New Jersey, United States

Suffolk OB-GYN; 🇺🇸 Port Jefferson, New York, United States

ClinSite; 🇺🇸 Ann Arbor, Michigan, United States

Dial Research Associates, Inc.; 🇺🇸 Nashville, Tennessee, United States

Lynhurst Clinical Research; 🇺🇸 Winston-Salem, North Carolina, United States

Women's Healthcare Associates dba Rosemark WomenCare Specialists; 🇺🇸 Idaho Falls, Idaho, United States