Pharmacodynamic Study of TPN171H Tablets in Patients With Mild to Moderate Erectile Dysfunction

Study Overview
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Brief Summary
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This study is a randomized, double-blind, placebo-controlled, two-cohort, three-cycle crossover (at least a 5-day cleaning period per cycle), and a multicenter clinical trial design.

Detailed Description
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This study is a randomized, double-blind, placebo-controlled, two-cohort, three-cycle crossover (at least a 5-day cleaning period per cycle), and a multicenter clinical trial design. The pharmacodynamic effects of different doses of TPN171H tablets on mild to moderate male patients with erectile dysfunction were evaluated by penile plethysmography (RigiScan PlusTM technique) using audiovisual sexual stimulation (AVSS).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Two-cohort, Three-way Crossover Clinical Trial to Evaluate the Pharmacodynamic Effect of Different Doses of TPN171H Tablets in Mild to Moderate Male Erectile Dysfunction

Conditions
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Erectile Dysfunction

Intervention / Treatment
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* Drug: TPN171H 2.5mg
* Drug: TPN171H 5mg
* Drug: TPN171H 10mg
* Drug: Placebo 5mg
* Drug: Placebo 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years to 65 years (inclusive) Males with ED at least 6 months, meets the diagnosis of mild and moderate erectile dysfunction，8≤IIEF-5 ≤ 21 Patients who are willing to stay away from any other medicines or treatments for ED during this study period Patients (including partners) 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 who have a history of hypersensitivity to other PDE5 inhibitors or TPN171H 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 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 not responded to PDE5 inhibitors or who have an adverse reaction leading to discontinuation CYP3A4 potent inhibitors, potent inducers, and moderate inducers (except topical drugs) should be used within 28 days before the start of treatment or during the trial period Subjects who are taking nitrate or NO donor drugs, anti-androgens, guanylate cyclase agonists, or other drugs or treatments for the treatment of ED and cannot be discontinued Patients with the following cardiovascular disease: Myocardial infarction or shock, or life-threatening arrhythmia within the last 6 months; Unstable angina or angina occurring during sexual intercourse within the last 3 months; Received coronary artery bypass grafting or percutaneous coronary intervention within the last 3 months；New York Heart Association Class 2 or greater heart failure in the last 6 months Uncontrolled hypotension (<90/60mmHg), uncontrolled hypertension(≥160/95mmHg) Diabetic patients whose FBS is over 1.5 fold of normal value, or whose HbA1c >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 Patients with a history of severe central nervous system injury or peripheral muscular neurological disease in the past 6 months Patient with a history of malignancy Patients with significant neurological abnormalities Patients with alcohol addiction Patients with persistent abuse of drugs of dependence Patients who have a childbirth plan during the trial period and within 3 months after the trial Patients who are participating in the past 3 months from any other clinical trial (except those who have participated in the clinical trials of this product before) 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: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>N=14 subjects receive 2.5 mg TPN171H and 10 mg Placebo for Period 1; 5 mg TPN171H and 10 mg Placebo for Period 2 ; 10 mg Placebo and 5 mg Placebo for Period 3. | Drug: TPN171H 2.5mg<br>* TPN171H 2.5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: TPN171H 5mg<br>* TPN171H 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 5mg<br>* Placebo 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 10mg<br>* Placebo 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>|
| Experimental: Sequence 2<br>N=14 subjects receive 5 mg TPN171H and 10 mg Placebo for Period 1; 10 mg Placebo and 5 mg Placebo for Period 2 ; 2.5 mg TPN171H and 10 mg Placebo for Period 3. | Drug: TPN171H 2.5mg<br>* TPN171H 2.5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: TPN171H 5mg<br>* TPN171H 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 5mg<br>* Placebo 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 10mg<br>* Placebo 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>|
| Experimental: Sequence 3<br>N=14 subjects receive 10 mg Placebo and 5 mg Placebo for Period 1; 2.5 mg TPN171H and 10 mg Placebo for Period 2; 5 mg TPN171H and 10 mg Placebo for Period 3. | Drug: TPN171H 2.5mg<br>* TPN171H 2.5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: TPN171H 5mg<br>* TPN171H 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 5mg<br>* Placebo 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 10mg<br>* Placebo 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>|
| Experimental: Sequence 4<br>N=14 subjects receive 5 mg TPN171H and 10 mg Placebo for Period 1; 10 mg TPN171H and 5 mg Placebo for Period 2; 10 mg Placebo and 5 mg Placebo for Period 3. | Drug: TPN171H 5mg<br>* TPN171H 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: TPN171H 10mg<br>* TPN171H 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 5mg<br>* Placebo 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 10mg<br>* Placebo 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>|
| Experimental: Sequence 5<br>N=14 subjects receive 10 mg TPN171H and 5 mg Placebo for Period 1; 10 mg Placebo and 5 mg Placebo for Period 2; 5 mg TPN171H and 10 mg Placebo for Period 3. | Drug: TPN171H 5mg<br>* TPN171H 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: TPN171H 10mg<br>* TPN171H 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 5mg<br>* Placebo 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 10mg<br>* Placebo 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>|
| Experimental: Sequence 6<br>N=14 subjects receive 10 mg Placebo and 5 mg Placebo for Period 1; 5 mg TPN171H and 10 mg Placebo for Period 2; 10 mg TPN171H and 5 mg Placebo for Period 3. | Drug: TPN171H 5mg<br>* TPN171H 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: TPN171H 10mg<br>* TPN171H 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 5mg<br>* Placebo 5mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>Drug: Placebo 10mg<br>* Placebo 10mg is recommended to take warm water on an empty stomach (2 hours or more after dinner)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of penile erections of greater than or equal to 60% rigidity as assessed by penile plethysmography (RigiScan PlusTM). |  | Baseline and during audiovisual sexual stimulation（60minutes） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The starting time of penile erections of greater than or equal to 60% rigidity |  | Baseline and during audiovisual sexual stimulation（60minutes） | 
| Duration of penile erections of greater than or equal to 60% rigidity as assessed by penile plethysmography (RigiScan PlusTM). |  | Baseline and during audiovisual sexual stimulation（minutes） | 
| Percentage increase in penile enlargement |  | Baseline and during audiovisual sexual stimulation（60minutes） | 
| The incidence of penile erection rigidity grade ≥ grade III. |  | Baseline and during audiovisual sexual stimulation（60minutes） |