A Multi-center Clinical Study on the Efficacy and Safety of Kuntai Capsule Alone and in Combination With Hormones in the Treatment of Early-onset Hypoovarian Function
Phase: PHASE4
Conditions: Primary Ovarian Insufficiency
Sponsor: Affiliated Hospital of Nantong University

A Multi-center Clinical Study on the Efficacy and Safety of Kuntai 
Capsule Alone and in Combination With Hormones in the Treatment 
of Early-onset Hypoovarian Function 
 
NCT05021094 
Date : August 4 , 2021 
Research Proposal Summary 
Scheme 
number 
HYKT18017S 
Scheme name 
A Multi-center Clinical Study on the Efficacy and Safety of Kuntai Capsule Alone and in 
Combination With Hormones in the Treatment of Early-onset Hypoovarian Function 
Version 
number/date 
Version 2.1 , June 18 , 2021 
sponsor 
Shanghai Haitian Pharmaceutical Technology Development Co., Ltd. 
Clinical 
trial 
staging 
Post-marketing clinical re-evaluation 
test drug 
Heyan Kuntai Capsules 
(Z20000083), each0.5g, was produced by Guiyang Xintian 
Pharmaceutical Co., Ltd. 
Indications 
POI (including subclinical stage) 
Test purposes 
To evaluate the efficacy and safety of Heyan Kuntai Capsules alone or in combination with 
hormone therapy in patients with POI (including subclinical stage) in improving ovarian function . 
Research 
design 
Prospective, multicenter, randomized, controlled clinical trial design 
total 
number 
of cases 
It is planned to complete 120 cases (considering the 20% dropout rate, at least 150 cases need to be 
enrolled) 
number 
of 
research 
6 _ 

centers 
Study period 
24 months 
research 
object 
Diagnostic criteria : 
The diagnostic criteria for premature ovarian insufficiency (POI) refer to the "2017 Chinese 
Expert Consensus on Clinical Diagnosis and Treatment of Premature Ovarian Insufficiency" and 
"2016 Expert Consensus on Hormone Supplementation Therapy for Premature Ovarian 
Insufficiency"; including: (1) Age <40 years old; (2) oligomenorrhea or amenorrhea for at least 4 
months; (3) at least 2 times serum basal follicle-stimulating hormone (FSH) > 25 IU/L (interval > 4 
weeks). Subclinical POI: FSH level is 15~25 IU/L, which is a high-risk group. 
The diagnostic criteria for premature ovarian failure (POF) refer to the "2017 Chinese Expert 
Consensus on Clinical Diagnosis and Treatment of Premature Ovarian Insufficiency", which refers 
to amenorrhea, FSH>40IU/L, and decreased estrogen levels before the age of 40, accompanied by 
varying degrees of perimenopause Stage symptoms are the terminal stage of POI. 
standard constrain: 
1. 18 years old ≤ age < 40 years old; 
2. At least two (>4 weeks interval) basal FSH≥15IU/L, with or without oligomenorrhea or 
menopause. 
3. Informed consent, voluntary experiment. 
Exclusion criteria: 
1. 
pregnant and lactating patients; 
2. 
Patients with endometriosis , adenomyosis , endometrial lesions ( submucosal fibroids , 
endometrial polyps, etc.), uterine fibroids >4cm or hysterectomy ; 
3. 
Patients with known or suspected history of breast cancer and estrogen-dependent 
malignancies; 
4. 
a personal history of venous thromboembolism ( VTE ) or with a high risk of VTE (including 
body mass index > 30 kg/m 2 , smoking, family history of thrombophilia); 
5. 
Porphyria patients; 
6. 
Patients with serious primary diseases such as cardiovascular, liver, kidney, hematopoietic 
system or mental illness; 

7. 
Patients who are participating in other clinical trials or have participated in other clinical trials 
within the past three months; 
8. 
Patients with suspected or real history of alcohol and drug abuse; 
9. 
Known allergy to the investigational drug or its components; 
10. Other patients deemed unsuitable for participation in this trial by the investigator. 
Note: Patients who were receiving hormone replacement therapy at the time of recruitment were 
required to take at least a 3 -month suspension of medication to participate in this trial. 
Trial grouping 
and 
medication 
1 POI patient 
According to the random sequence generated by computer, eligible patients were randomly 
assigned to Kuntai group , control group and combination group according to 1: 1 : 1 . 
(A) Kuntai group ( 30 cases): Oral Kuntai capsules, 4 capsules at a time, 3 times a day , 28 days as 
a course of treatment, taking medicine for 3 courses ; 
(B) Control group ( 30 cases): the sequential regimen of estrogen and progesterone was used, and 
the drug was estradiol tablets/estradiol dydrogesterone tablets (fenmetone), and red tablets 
(estradiol, 2 mg/d), and gray tablets (estradiol , 2 mg/d, dydrogesterone, 10 mg/d) were taken for 
the next 14 days , 28 days as a course of treatment, and three courses of medication were taken. 
(C) Combination group ( 30 cases): On the basis of hormone therapy, Kuntai Capsules were added, 
and the dose was the same as that of Kuntai group and hormone group for 3 months. 
2. Patients with POI in subclinical stage : self-control before and after experiment group (30 
cases): Oral Kuntai capsules, 4 capsules at a time , 3 times a day, 28 days as a course of treatment, 
taking medicine for 3 courses of treatment. 
Treatment and 
follow-up 
1.Course of treatment: 28 days as a course of treatment, taking medicine for 3 courses of treatment 
2. Visit points: before treatment (stage V 0 , screening period, days -35 to 0), baseline period (day 
0), after 3 months of treatment (stage V 1 , days 84 to 105 ), drug withdrawal 3 months later ( V2 
stage , 168-210 days) and 6 months after drug withdrawal (V 3 stage , 252-315 days ) . 
Specific inspection items include: 
1. The patient 's hormone levels (basal FSH, LH, E 2 ) were detected in V 0 , V 1 , and V 2 stages ; 
2 Anti-Müllerian hormone ( AMH ) was detected in patients at V 0 and V 1 stages ; 
3 The patients underwent B-ultrasound at V 0 and V 1 stage to monitor the follicular development , 

record the number of antral follicles ( AFC ), ovarian hemodynamic parameters (PSV, EDV, S/D, RI 
and PI); 
4. Modified Kupperman score was performed in V 0 , V 1 and V 2 stage; 
5 Pregnancy was recorded at the V 2 outpatient follow-up for patients with reproductive needs ; 
6 patients at V 0 and V 1 to detect blood routine (RBC, WBC, PLT, HGB) , liver function (ALT, 
AST) and renal function (BUN, Cr) , and recorded adverse events. 
 
Note: 
1 Basal follicle-stimulating hormone ( FSH ) ≥ 15IU/L at first visit in patient V0 , and if other 
inclusion criteria are met, if the patient has a history of testing with a baseline FSH ≥ 15 IU/L in 
the past (interval> 4 weeks) , he or she can be included in this study and drug therapy can be 
started; (Interval > 4 weeks) If the basic FSH ≥ 15 IU/L has not been diagnosed , the patient is 
required to visit the hospital again after 4 weeks. If the basic FSH is still ≥ 15 IU/L , they can be 
included in this study and drug therapy can be started. 
2 For patients with regular menstrual periods, the basal FSH and antral follicle count ( AFC ) 
should be followed up on the 2nd to 4th day of the menstrual cycle. If the patient has menstrual 
cramps after the follow-up and has not exceeded the visit window, they are required to re-examine 
on the 2nd to 4th day of the menstrual cycle and record the examination data. 
study endpoint Primary endpoint : FSH, modified Kupperman score  
Secondary endpoints :  
(1) FSH/LH, LH , E2 ; ( 2 ) Antral follicle count ( AFC ); (3) Anti- Müllerian hormone ( AMH ); ( 4 ) 
Proportion of patients with normal menstruation; ( 5 ) Ovarian hemodynamics parameters (PSV, 
EDV, S/D, RI and PI); ( 6 ) Clinical pregnancy rate (patients with reproductive needs). 
security 
indicators 
1 Blood routine (RBC, WBC, PLT, HGB) , liver function (ALT, AST) and renal function (BUN, 
Cr) ; 
2 Patient adverse events were recorded.