Efficacy and Safety of TPN171H in the Patients With Erectile Dysfunction

Study Overview
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Brief Summary
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This is an exploratory clinical study to presume the optimum usage and dosage for a therapeutic confirmatory study by evaluating the efficacy and safety of TPN171H 5mg, 10mg, 20mg or placebo administered orally in patients with erectile dysfunction. In conclusions, Patients with erectile dysfunction (ED) were administered placebo, TPN171H 5mg, 10mg or 20mg 30 minutes to 4 hours before sexual intercourse for 8 weeks.

Detailed Description
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This is a Phase II study in 240 ED patients, which consists of 3 part: 1) a 4-week run-in period without any ED treatment; 2)randomization to 8 weeks of treatment with TPN171H or placebo; and 3) a 1-week follow-up period for continued adverse event monitoring. The effects of TPN171H on ED will be evaluated using the IIEF-EF and SEP diaries. The IIEF-EF will be administered at baseline and at 4-week intervals following initiation of treatment, meanwhile the SEP diary will be completed by patients after each sexual attempt throughout the study.

Official Title
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A Multi-Center ,Randomized, Double-Blind, Placebo-Controlled, Dose-Exploring Study to Evaluate the Efficacy and Safety of TPN171H in China Male Patients With Erectile Dysfunction

Conditions
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Erectile Dysfunction

Intervention / Treatment
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* Drug: TPN171H
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients aged ≥22 with ED, defined as an inability to achieve or maintain a penile erection sufficient for satisfactory sexual intercourse, evident for at least 3 months; Patients whose IIEF-EF domain score is < 26; Patients in a stable, heterosexual relationship for at least 3 months and during the study; Patients who are willing to stay away from any other medicines or treatments for ED during this study period; Patients who are willing to have 4 or more attempts of sexual intercourse each month, demonstrated compliance with the study protocol, including drug administration, diary completion, and scheduled study visits, during the qualifying trial; Patients who are willing to take proper contraceptive during the study and within 3 months after the study completed; Patients who have voluntarily decided to participate in this study, and signed the informed consent form. Exclusion Criteria: Patients with anatomical malformations of the penis; Patients with primary hypoactive sexual desire; Patients with ED, which is caused by any other primary sexual disorder, like hypopituitarism, hypothyroidism, or hypogonadism. Patients with ED ,which is caused by spinal injury or have had a radical prostatectomy or other surgery ; Patients who have a penile implant; Patients who have a history of hypersensitivity to other PDE5 inhibitors or who have not responded to them; Patients with the following cardiovascular disease: Myocardial infarction or stroke within the last 6 months; Unstable angina or angina occurring during sexual intercourse; New York Heart Association Class 2 or greater heart failure in the last 6 months; Uncontrolled hypotension (<90/60mmHg), or uncontrolled hypertension (≥160/95mmHg); Orthostatic hypotension. Patients administered with the following medications: Nitrate/Nitric oxide (NO) donors; Androgens, anti-androgen, trazodone; Agents that significantly affect the CYP3A4 intermediary metabolism. Diabetic patients whose FBS is over 1.5 fold of normal value, or whose HbA1c exceeds 9%, or with diabetes complications, such as diabetic nephropathy, peripheral neuropathy; Patients with hepatic or renal dysfunction as per the following: AST, ALT≧2*ULN, serum creatinine exceeds 20% of the upper limit of normal value; Patients with active gastrointestinal ulcers and bleeding disorders; Patients who have a history of NAION, or with a known genetically degenerative retinopathy, including retinitis pigmentosa; Patients who have a history of sudden decrease or loss of hearing; Patient with a history of malignancy; Patients with a major refractory psychiatric disorder or significant neurological abnormalities; Patients with alcohol addiction or persistent abuse of drugs of dependence; Patients who are participating or discontinued participation in the past 3 months from any other clinical trial, or are planning to father a baby or are in a relationship with a pregnant partner. For other reasons besides the aforementioned cases, patient whose participation is deemed inappropriate due to clinically significant findings according to the medical decision of the principal investigator or the study personnel.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TPN171H 5mg group<br>TPN171H 5mg tablet + Placebo 10mg 2 tablets | Drug: TPN171H<br>* Pharmaceutical form;tablets Route of administration:;oral;Administered 30 minutes to 4 hours prior to initiation of sexual activity for a duration of 8 weeks to use no more than one dose in any 24-hour period<br>* Other names: Simmerafil;|
| Experimental: TPN171H 10mg group<br>TPN171H 10mg tablet + Placebo 5mg tablet+ Placebo 10mg tablet | Drug: TPN171H<br>* Pharmaceutical form;tablets Route of administration:;oral;Administered 30 minutes to 4 hours prior to initiation of sexual activity for a duration of 8 weeks to use no more than one dose in any 24-hour period<br>* Other names: Simmerafil;|
| Experimental: TPN171H 20mg group<br>TPN171H 10mg 2 tablets + Placebo 5mg tablet | Drug: TPN171H<br>* Pharmaceutical form;tablets Route of administration:;oral;Administered 30 minutes to 4 hours prior to initiation of sexual activity for a duration of 8 weeks to use no more than one dose in any 24-hour period<br>* Other names: Simmerafil;|
| Placebo Comparator: Placebo group<br>Placebo 5mg tablet+ Placebo 10mg 2 tablets | Drug: placebo<br>* Pharmaceutical form;tablets Route of administration:;oral;Administered 30 minutes to 4 hours prior to initiation of sexual activity for a duration of 8 weeks to use no more than one dose in any 24-hour period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the International Index of Erectile Function - Erectile Function Domain (IIEF-EF) at Week 8 | The primary efficacy variable was the change in the EF domain scores of the IIEF questionnaire from baseline, calculated by comparing total scores from questions 1-5 and 15 from the IIEF questionnaire . | baseline and 8 weeks | 
| Change From Baseline in Question 2 of the Patient Sexual Encounter Profile (SEP) Diary at Week 8 in Percentage of Yes Responses | Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Question 2. Were you able to insert your penis into your partner's vagina when you are trying to have sex ? Data are presented as the mean percentage of yes responses per participant. | baseline and 8 weeks | 
| Change From Baseline in Question 3 of the Patient Sexual Encounter Profile (SEP) Diary at Week 8 in Percentage of Yes Responses | Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Question 3. Did your erection last long enough for you to have successful intercourse? Data are presented as the mean percentage of yes responses per participant. | baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Week and 8 Week Endpoint in International Index of Erectile Function (IIEF),Orgasmic Functions | Self-reported Orgasmic Functions over the past 4 weeks. Scores range from 0 (low/no satisfaction) to 5 (high satisfaction), thus the 2 questions of the IIEF-OF domain range from 0 to 10. | baseline ,4 weeks and 8 weeks | 
| Change From Baseline to 4 Week and 8 Week Endpoint in International Index of Erectile Function (IIEF) ,Sexual Desire | Self-reported Sexual Desire over the past 4 weeks. Scores range from 0 (low/no satisfaction to 5 (high satisfaction), thus the 2 questions of the IIEF-SD domain range from 0 to 10. | baseline ,4 weeks and 8 weeks | 
| Change From Baseline to 4 Week and 8 Week Endpoint in International Index of Erectile Function (IIEF),Intercourse Satisfaction | Self-reported intercourse satisfaction over the past 4 weeks. Scores range from 0 (low/no satisfaction) to 5 (high satisfaction), thus the 3 questions of the IIEF-IS domain range from 0 to 15. | baseline ,4 weeks and 8 weeks | 
| Change From Baseline to 4 Week and 8 Week Endpoint in International Index of Erectile Function (IIEF), Overall Satisfaction | Self-reported overall satisfaction over the past 4 weeks. Scores range from 0 (low/no satisfaction to 5 (high satisfaction), thus the 2 questions of the IIEF-OS domain range from 0 to 10. | baseline ,4 weeks and 8 weeks | 
| Change From Baseline in Question 2 of the Patient Sexual Encounter Profile (SEP) Diary at Week 4 in Percentage of Yes Responses | Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Question 2. Were you able to insert your penis into your partner's vagina? Data are presented as the mean percentage of yes responses per participant. | baseline and 4 weeks | 
| Sexual Encounter Profile (SEP) Diary, Question 3 Change From Baseline to Week 4 in Percentage of Yes Responses | Assessed was the mean change from baseline in the percentage of Yes responses to the SEP diary Question 3. Did your erection last long enough for you to have successful intercourse? Data are presented as the mean percentage of yes responses per participant. | baseline and 4 weeks | 
| Change From Baseline in the International Index of Erectile Function - Erectile Function Domain (IIEF-EF) ≥26 at Week 8 | Assessed was the changes in the number of subjects whose IIEF domain score at the 8th week visit was ≥26. | baseline ,4 weeks and 8 weeks | 
| Subgroup analysis based on ED severity categories: severe,0-10; moderate,11-16; mild,17-25. | Subgroup analysis based on ED severity categories: severe,0-10; moderate,11-16; mild,17-25. | baseline ,4 weeks and 8 weeks | 
| Subgroup analysis based on the time intervals between meal and medication. | Subgroup analysis based on the time intervals between meal and medication. | baseline ,4 weeks and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erectile Dysfunction, TPN171H, Simmerafil