Clinical trial NCT04170790: Evaluation of Drug Interactions of Saxagliptin With Sildenafil in Healthy Volunteers
Official title: Evaluation of Drug Interactions of Saxagliptin With Sildenafil in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Erectile Dysfunction With Diabetes Mellitus
Drug Interaction
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2019-11-20
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: SEQUENTIAL
Intervention model description: Eighteen healthy volunteers will be recruited in Sequential, single center study to determine pharmacokinetic parameters of Saxagliptin, and sildenafil,(AUC0→∞), (AUC0→t); Cmax; tmax; t½, k; ka) will be measured using validated LC-MS/MS method. Therapeutic doses will be given to volunteers as follows: Sildenafil 50 mg single dose on day 1, then washout period from day 2 till day 8. Saxagliptin 5 mg once/day will be given from day 9 till day 12, then on day 13 the two drugs will be co-administered. Blood samples (5ml) for pharmacokinetic analysis will be collected on days 1 and 13 for Sildenafil as well as on days 12 and 13 for Saxagliptin
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Patients with diabetes are three times more likely to develop erectile dysfunction (ED), and longer duration of diabetes is strongly associated with ED. The possibility of pharmacokinetic interactions may occur as the two drugs are metabolized by hepatic CYP3A4 and their co administration may affect their plasma concentrations. the aim of work is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of Saxagliptin, a CYP3A4 substrate Subjects and Methods: Eighteen healthy volunteers will be recruited in Sequential, single center study to determine pharmacokinetic parameters of Saxagliptin, and sildenafil,(AUC0→∞), (AUC0→t); Cmax; tmax; t½, k; ka) will be measured using validated LC-MS/MS method. Therapeutic doses will be given to volunteers as follows: Sildenafil 50 mg single dose on day 1, then washout period from day 2 till day 8. Saxagliptin 5 mg once/day will be given from day 9 till day 12, then on day 13 the two drugs will be co-administered. Blood samples (5ml) for pharmacokinetic analysis will be collected on days 1 and 13 for Sildenafil as well as on days 12 and 13 for Saxagliptin.


Eligibility criteria: Inclusion Criteria:

1. Age 18-45 years.
2. Ideal weight within the normal range according to accepted life tables.
3. Non-contributory history and normal physiological examination.
4. Laboratory data within normal limits.
5. Performance and compliance.
6. The subjects should be without known history of alcohol or drug abuse problems and should preferably be non-smokers.
7. The volunteers will be asked to provide a complete medical history, and complete a physical examination, laboratory tests (hematology, clinical chemistry, urinalysis serology (including hepatitis B surface antigen, anti-hepatitis C virus and antihuman immunodeficiency virus antibody).

Exclusion Criteria:

1. A known hypersensitivity to the drug.
2. Gastrointestinal diseases.
3. Auto immune diseases.
4. Renal diseases or dysfunction.
5. Cardiovascular disease of any type.
6. Pancreatic disease including diabetes.
7. Hepatic disease.
8. Hematological, osteopathic, or pulmonary disease.
9. History of alcoholism or drug abuse.
10. Serious Psychological illness.
11. Positive HIV-I.
12. Smoking (if including they should be identified).
13. Abnormal (out of range) laboratory values.
14. Subject who have taken any medication (Rx or OTC) less than two weeks of the trials starting date.
15. Subject who have donated blood or who have been in multiple dosing studies requiring a large volume of blood (more than 500 ml) to be drawn within six weeks preceding the start of the trials.
16. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.
17. Treatment with any known enzyme-inducing / inhibiting agents within 30 days prior to the start of the study and throughout the study.

Primary outcomes:
measure: Cmax
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: (AUC0→∞)
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: (AUC0→t)
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: tmax;
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: T½
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: Ke
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: ka
timeFrame: pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.
measure: Blood Pressure
timeFrame: measured before dosing and at 2, 4, 6, 8, and 10 hours after drug administration on each day of blood sampling
measure: Heart Rate
timeFrame: measured before dosing and at 2, 4, 6, 8, and 10 hours after drug administration on each day of blood sampling
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Mansour RY, ElBorolossy R, Shaheen SM, Sabri NA. Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers. Eur J Clin Pharmacol. 2022 Dec;78(12):1935-1944. doi: 10.1007/s00228-022-03397-w. Epub 2022 Oct 10.