A study comparing the level of absorption of sildenafil from Sildenafil 100 mg Oral Films versus Viagra® 100 mg tablets and the effect of food on absorption of sildenafil from Sildenafil 100 mg Oral Films in healthy men
| ISRCTN | ISRCTN13297409 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13297409 |
| Secondary identifying numbers | ISS-P7-882 (Sponsor Project No 17CDN-SDF02) |
- Submission date
- 13/07/2018
- Registration date
- 04/09/2018
- Last edited
- 12/03/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
A new oral film containing sildenafil citrate, the active ingredient in Viagra, which is used to treat erectile dysfunction (ED), has been recently developed. It dissolves very rapidly in the oral mouth, with no need for drinking or chewing, thus providing an alternative to the marketed solid oral forms (tablets) in the treatment of ED. This study aims to investigate whether the oral film is absorbed as well as the solid oral form, and to determine if food has an effect on the absorption of this new film.
Who can participate?
Healthy men aged 18-45 years
What does the study involve?
The study has three periods, and participants will be randomly allocated into one section and then will rotate through each period such that every participant completes all periods of the trial but the order will vary depending on the period they are initially randomised into:
Period A: a single dose of Sildenafil 100 mg Oral Film after a high-fat breakfast
Period B: a single dose of Sildenafil 100 mg Oral Film after fasting overnight
Period C: a single dose of Sildenafil (Viagra®) 100 mg film-coated tablet after fasting overnight
There will be a break of at least 7 days between the periods.
The blood level of sildenafil is measured pre-dose (0) and 10, 15, 20, 30, 40, 50 minutes, 1 hour, 1:20, 1:40, 2, 2:20, 2:40, 3, 4, 5, 6, 8, 10, 12, 16 and 24 hours after the dose.
What are the possible benefits and risks of participating?
There are no known benefits or risks to participants taking part in this study.
Where is the study run from?
Algorithme Pharma Mount-Royal, Quebec, Canada.
When is the study starting and how long is it expected to run for?
February 2017 to March 2018
Who is funding the study?
IBSA Institut Biochimique SA (Switzerland)
Who is the main contact?
Dr Eric Sicard
esicard@algopharm.com
Contact information
Scientific
Algorithme Pharma, 1200 Beaumont Ave
Mount-Royal, Quebec
H3P 3P1
Canada
Study information
| Study design | Interventional single-center single dose laboratory-blinded 3-period 3-sequence, randomised crossover study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details below to request a participant information sheet |
| Scientific title | Single Dose Crossover Comparative Bioavailability Study under Fasting Conditions and Food Effect Study of Sildenafil 100 mg Oral Films Versus Viagra® (Sildenafil) Tablets in Healthy Male Volunteers |
| Study objectives | To determine whether Sildenafil 100 mg oral film is bioequivalent to Viagra® 100 mg film-coated tablet under fasting conditions and evaluate the food effect on the absorption of sildenafil from Sildenafil 100 mg oral film. |
| Ethics approval(s) | IRB Services (372 Hollandview Trail, Suite 300, Aurora, Ontario, Canada L4G 0A5), 13/06/2017, Pro00021969 Health Canada, 23/06/2017, 206698 |
| Health condition(s) or problem(s) studied | Erectile dysfunction |
| Intervention | Three treatments are administered as a single 100 mg oral dose. Each of the 45 healthy male subjects receives in each period one of the following treatments, according to a randomized, 3-period, crossover design. Subjects are assigned to the order of treatments in the 3 study periods according to the randomisation list, and are randomised to receive one of the treatments in period 1, one in period 2 and one in period 3. Subjects are assigned a number at the check-in of period 1. Each subject retains this number throughout the study. The order of investigational product administration is sequentially assigned from a computer-generated randomised list. Treatment-1: Sildenafil 100 mg Oral Film, single oral dose in fed conditions (Thirty minutes after the start of a standardized high-fat, high-calorie breakfast) Treatment-2: Sildenafil 100 mg Oral Film, single oral dose in fasting conditions Treatment-3: Sildenafil (Viagra®) 100 mg film-coated tablet, single oral dose in fasting conditions The drug administrations is separated by at least 7 calendar days. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Sildenafil IBSA 100 mg oral film Viagra® (sildenafil citrate) 100 mg film-coated tablet |
| Primary outcome measure | Pharmacokinetic parameters (Cmax, AUC, Tmax, Thalf, λZ) for the absorption of sildenafil. The concentration of sildenafil in plasma is measured at the following time-points: pre-dose (0) and 10, 15, 20, 30, 40, 50 min, 1 h, 1:20, 1:40, 2, 2:20, 2:40, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after the dose in each of the three study periods. Each study period is separated by at least 7 calendar days. Plasma samples are assayed for sildenafil using a validated high performance liquid chromatography (HPLC) method with tandem mass spectrometry (MS/MS) detection. The lower limit of quantitation (LOQ) and upper limit of quantitation (ULQ) are 1.00 and 1000.00 ng/ml for sildenafil. |
| Secondary outcome measures | 1. Record of adverse events throughout the study. Any new illness, or worsening of a concomitant illness, and the medically relevant abnormalities in laboratory tests, physical examination and in the measurements of vital signs performed after drug administration or at the end of the study are to be recorded as adverse events. The period of observation of adverse events extends from the pre-trial evaluation until the collection of the last blood sample of the study. During the study, all adverse events spontaneously reported by the subject, observed by the clinical staff, or elicited by general questioning are recorded at any time. Subjects are questioned on their health status at the beginning of each study period and before each departure from the clinical site. 2. Vital signs: Blood pressure, pulse rate and body temperature are measured and recorded prior to each drug administration. Blood pressure and pulse rate are also recorded approximately 1, 2 and 4.5 hours after each drug administration. 3. Physical examination, performed at screening and at final visit after the last study period. 4. Laboratory analysis: haematology, blood chemistry and urinalysis laboratory tests performed at screening and at final visit after the last study period. |
| Overall study start date | 24/02/2017 |
| Completion date | 22/03/2018 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 45 Years |
| Sex | Male |
| Target number of participants | 45 |
| Key inclusion criteria | 1. Aged 18-45 years 2. BMI of 18.5 - 30.0 kg/m² 3. Non-smoker or ex-smoker 4. No clinically significant diseases or findings upon physical examination and/or clinical laboratory evaluations (hematology, general biochemistry, lipid profile, ECG and urinalysis) 5. Provided signed informed consent |
| Key exclusion criteria | 1. Presence or history within 28 days of any tongue piercings 2. Presence of partials, braces or dentures 3. History of significant hypersensitivity to sildenafil or related products (including excipients of formulations) 4. History of severe hypersensitivity reactions to any drugs 5. Significant gastrointestinal, liver or kidney disease, or any other conditions known to: 5.1. Interfere with the absorption, distribution, metabolism or excretion of drugs 5.2. Potentiate or predispose to undesired effects such as severe liver failure, acute or chronic liver dysfunction or cholestatic jaundice 6. History of significant gastrointestinal, liver or kidney disease that may have affected drug bioavailability 7. Significant cardiovascular, pulmonary, hematological, neurological, psychiatric, endocrine, immunological or dermatological disease 8. Suicidal tendencies, severe depression, state of confusion or other clinically relevant psychiatric diseases 9. History of or disposition to seizures 10. Presence of out-of-range cardiac interval on the screening ECG or other clinically significant ECG abnormalities 11. Use of organic nitrate medications in the previous 28 days 12. History of vision or hearing problems related to the PDE5 inhibitor pharmacological class 13. Presence or history of priapism 14. Anatomical deformation of the penis 15. History of ophthalmological disease, such as non-arteritic anterior ischemic optic neuropathy or retinitis pigmentosa 16. Known presence of rare hereditary problems of: 16.1. Galactose and/or lactose intolerance 16.2. Lactase deficiency 16.3. Glucose-galactose malabsorption 17. Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol (acute or chronic)) 18. Positive screening for alcohol and/or drug abuse 19. Use of enzyme modifying drugs in the previous 28 days, including: 19.1. Strong inhibitors of CYP enzymes (e.g. cimetidine, fluoextine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) 19.2. Strong inducers of CYP enzymes (e.g. barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St Johns Wort) 20. History of tuberculosis and/or prophylaxis for tuberculosis 21. Positive results to the following tests: 21.1. HIV Ag/Ab Combo 21.2. Hepatitis B surface antigen (HBsAG (B) (hepatitis B)) 21.3. Hepatitis C Virus (HCV (C)) 22. Taken sildenafil in the previous 28 days 23. Donated 500 ml or more of blood in the previous 56 days |
| Date of first enrolment | 15/06/2017 |
| Date of final enrolment | 01/08/2017 |
Locations
Countries of recruitment
- Canada
Study participating centre
Mount-Royal, Quebec
H3P 3P1
Canada
Sponsor information
Industry
Via del Piano
Pambio-Noranco
6915
Switzerland
"ROR" |
https://ror.org/051tj3a26 |
|---|
Funders
Funder type
Not defined
No information available
Results and Publications
| Intention to publish date | 01/12/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | Full study data will be stored in a database of the sponsor. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 08/03/2019 | No | No |
Additional files
Editorial Notes
12/03/2019: The basic results of this trial have been uploaded as an additional file.
