Phase 2A Clinical Trial Evaluating the Potential Activity... | NCT02713789

NCT02713789

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Dasman Diabetes Institute	OTHER
Ion Channel Innovations	INDUSTRY

Description Module

Detailed Description

This study is a double-blind, placebo controlled, parallel design, Phase 2A study evaluating the potential activity and safety of a single administration of hMaxi-K (8000 or 16000 µg) or placebo (PBS sucrose 20%) injected into the corpus cavernosum of the penis in men who have been unable to tolerate, do not wish to continue, or have had unsuccessful results with, prior therapy for ED.

The study population is men with erectile dysfunction attributable to an underlying, stable medical condition but who are otherwise in good health. The target population is men with erectile dysfunction and those who have been unable to tolerate, do not wish to continue, or have had unsuccessful results with, prior therapy for ED and with an erectile function domain score of IIEF < 21 at screening and baseline.

Following screening and study drug administration at Week 0 (Visit 2 [V2]), eligible participants will be evaluated at Weeks 1 (V3), 4 (V4), 8 (V5), 12 (V6), and 24 (V7). At each study visit, participants will have a physical examination including examination of the penis (all visits), vital signs, electrocardiogram (ECG) (all visits). Laboratory evaluations including chemistry and hematology will be done at V1, V3, V4, V6, and V7. Urinalysis will be done V1, V2 (prior to dosing), V3, V4, V6, and V7. Endocrine parameters and PTT, PT, sed rate and CRP will be evaluated at V1, V3, and V7. The participant will complete the erectile function domain of the IIEF and Sexual Encounter Profile (SEP) at screening/baseline and at V2, (SEP and IIEF at V2 prior to dosing) V3, V4, V5, V6, and V7. In all participants, plasma specimens will be collected to assay for the presence of hSlo DNA by PCR (V2-V7). These will be kept frozen at -20°C or less at the site for eventual assay by Sponsor.

The primary efficacy outcome measures will include the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), Questions 2 and 3 from SEP. The IIEF EF domain has a 30-point total score, where higher scores reflect better erectile function. SEP is a diary in which participants record each sexual attempt made throughout the study. The two questions from the Sexual Encounter Profile (SEP) deal with the ability to achieve vaginal penetration (SEP2), and the ability to maintain an erection long enough for successful intercourse (SEP3). The erectile function domain category of the IIEF will be used to evaluate the change in erectile status from baseline following administration of hMaxi-K. Change from baseline on the six questions of the IIEF's Erectile function domain category at every visit after administration of study drug will be calculated and compared among the two dose and one placebo groups.

Safety will be assessed by analysis of adverse experiences, and abnormal findings on clinical laboratory tests, electrocardiogram, and physical examinations.

6 months per participant (approximately 2 years to enroll all participants)

A total of 35 participants were planned to be enrolled; N=11 on 8000 µg; N=11 on 16000 µg; N=13 on placebo.

Both the safety data and data to assess activity will be presented as means and standard deviations or medians and ranges as appropriate for continuous data, and analyzed using either paired t- or Wilcox on Sign Rank tests for within group changes, and with mixed effects or marginal models to determine differences in trends among the three cohorts over time. Incidence of adverse events will be presented as relative frequencies within groups.

Label	Type	Description	Intervention Names
hMaxi-K	Active Comparator	Single Treatment/ two escalating dose levels (8000 µg and 16,000 µg injection). In each dose level, 11 participants will receive hMaxi-K and 6 will receive placebo (only one injection per each participant)	Drug: hMaxi-K Single Treatment/ 2 escalating dose levels (8000 µg and 16000 µg injection)
Placebo (PBS-20% sucrose)	Placebo Comparator	PBS-20% sucrose administered during two single treatment dose levels (8000 µg and 16000 µg) by injection (only one injection per each participant)	Drug: Placebo (PBS-20% sucrose)

Name	Type	Description	Arm Group Labels	Other Names
hMaxi-K Single Treatment/ 2 escalating dose levels (8000 µg and 16000 µg injection)	Drug		hMaxi-K	hMaxi-K URO-902

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Experiences as Measured by Changes in Physical Examination of the Penis	Physical examination of the penis included inspection and palpation.	up to Week 24 ± 3 days
Number of Participants With Significant Changes in Clinical Laboratory Parameters as Measured on Interval Blood and Urine Tests	Clinical significance was determined by the Investigator using central laboratory values.	up to Week 24 ± 3 days
Number of Participants With Significant Changes on the Cardiogram as Measured by Significant Prolongation of QT Intervals and Cardiac Rhythm	Clinical significance was determined by the Investigator using central laboratory values.	up to Week 24 ± 3 days

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in the Percentage of "Yes" Responses to Questions 2 and 3 of the Sexual Encounter Profile (SEP) at Week 24	SEP is a diary in which participants record each sexual attempt made throughout the study and is composed of 5 questions assessing sexual function. Two questions from the SEP deal with the ability to achieve vaginal penetration (Question 2: Were you able to insert your penis into your partner's vagina?), and the ability to maintain an erection (Question 3: Did your erection last long enough for you to have successful intercourse?). The number of "yes" response to each question in the SEP was computed as (Sum of all "yes" responses to respective SEP question /Total number of responses to that SEP question)*100. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eligible participants must meet the following inclusion criteria:
1. Signed Informed Consent
2. Be adult males over 18 years of age diagnosed with erectile dysfunction and whose ED is attributable to an underlying, stable medical condition such as hypertension and atherosclerosis, antihypertensive medication, type I and type II diabetes mellitus, pelvic surgery and pelvic radiation, cerebrovascular accidents (stroke), multiple sclerosis, and Parkinson's disease;
3. Participants must have been unable to have successful sexual intercourse for 3 months prior to study entry without specific ED therapy such as Vacuum Erection device (VED), ViagraTM (sildenafil), Cialis TM (tadalafil), MuseTM (alprostadil), or intracavernous injection therapy with an erectile function domain score of IIEF<21 at screening and baseline;
4. Have been unable to tolerate, do not wish to continue, or have had unsuccessful results with, prior therapy for ED, e.g., ViagraTM, intracavernous injection therapy, MuseTM, or VED;
5. If diabetic, documentation of HgA1c less than or equal to 8.0% prior to enrollment;
6. If receiving medication for hypertension, documentation of blood pressure has been stable on the same medication for at least 2 months prior to enrollment;
7. Be heterosexual and in a stable, monogamous relationship of at least six months duration;
8. Agree to attempt intercourse with their partner at least four times per month while participating in the study;
9. Agree not to use other treatments for ED while participating in this study;
10. Have screening laboratory values and ECG that are within the normal range. See exclusion criterion below.
11. A prior penile prosthetic implant;
12. Have a normal physical examination of the penis;
13. If participant had a radical prostatectomy a PSA <0.4 for at least one year documented by 2 measurements during the preceding year;
14. Be literate, able to give written informed consent, and comply with all study procedures and requirements.

Exclusion Criteria:

A history of sickle-cell disease, sickle cell trait, or any other medical condition that, in the judgment of the investigator, would contraindicate the administration of study medication or interfere with the study evaluations;
In the judgment of the investigator any condition that would interfere with participation in the study (including geographical inaccessibility), that would contraindicate the administration of study medication or interfere with the study evaluations.
Had within six months prior to enrollment any of the following:
- Myocardial infarction
- Cerebrovascular accident
- Uncontrolled hypertension (systolic >160 or diastolic >100mmHg)
- Arrhythmia
- Congestive heart failure (dyspnea on minimal exertion or while supine)
- Unstable angina (chest pain greater than three times weekly while on therapy)
- Required treatment with calcium channel, beta-blocker medication, nitrates, or anti-epileptic drugs;
Poorly controlled diabetes mellitus as defined by HgA1c > 8.0 mg% at time of enrollment;
Change in medication for diabetes or hypertension within 2 months of study enrollment;
Gonadal failure (testosterone < 200 ng/dl) not treated with hormone replacement;
History of malignancy except non-melanomatous skin cancers;
A life expectancy of less than 12 months;
An indwelling urethral catheter;
A prior penile prosthetic implant;
Received an investigational drug, investigational therapy, or other form of ED therapy, including approved treatments, within the past 30 days;
Peyronie's disease;
Any screening laboratory values outside of the normal laboratory range as defined by the central laboratory normal ranges and in the judgment of the investigator is considered clinically significant (hepatic biochemical markers [AST, ALT, GGT, alkaline phosphatase, and bilirubin] > twice the upper limit of the normal reference range may be accepted with written consent of the sponsor).
Any clinically significant ECG abnormality

NOTE: Sinus bradycardia of 50-59 bpm is permissible. Other abnormalities that can be normal variants (and considered clinically insignificant) may be permissible. However, participants with such abnormalities cannot be randomized without review of their medical history and prior written approval of the sponsor (or designee).

Facility	Status	City	State	ZIP	Country	Contacts
Dasman Diabetes Institute		Kuwait City	Dasman	1180	Kuwait

ID	Title	Description
FG000	hMaxi-K 8000 µg	Participants received a single injection of hMaxi-K 8000 micrograms (µg) into the corpus cavernosum of the penis.
FG001	hMaxi-K 16000 µg	Participants received a single injection of hMaxi-K 16000 µg into the corpus cavernosum of the penis.
FG002	Placebo	Participants received a single injection of matching placebo (PBS-20% sucrose) into the corpus cavernosum of the penis.

ID	Title	Description
BG000	hMaxi-K 8000 µg	Participants received a single injection of hMaxi-K 8000 micrograms (µg) into the corpus cavernosum of the penis.
BG001	hMaxi-K 16000 µg	Participants received a single injection of hMaxi-K 16000 µg into the corpus cavernosum of the penis.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Adverse Experiences as Measured by Changes in Physical Examination of the Penis

Physical examination of the penis included inspection and palpation.

Safety Population: all participants who were randomized to any of the treatment groups and who have received at least one dose of study treatment

Posted

Count of Participants

Participants

up to Week 24 ± 3 days

ID	Title	Description
OG000	hMaxi-K 8000 µg	Participants received a single injection of hMaxi-K 8000 micrograms (µg) into the corpus cavernosum of the penis.
OG001	hMaxi-K 16000 µg	Participants received a single injection of hMaxi-K 16000 µg into the corpus cavernosum of the penis.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 1, 2016	Jul 12, 2019	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Dec 14, 2017	Jul 12, 2019	SAP_001.pdf

ID	Term
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D012735	Sexual Dysfunction, Physiological

ID	Term
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics