Effect of KYG0395 on Primary Dysmenorrhea
Condition: Primary Dysmenorrhea
MeSH terms: Dysmenorrhea
Intervention: high dose KYG0395; lower dose KYG0395; Placebo
Intervention description: 3 KYG0395 capsules tid (morning, midday, and evening); 3 KYG0395 capsules 2 times a day (bid) (morning and evening) plus 3 capsules of placebo (midday); 3 capsules of placebo tid (morning, midday, and evening)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 280.0
Sex: Female
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: No

Summary:

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

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)