Bioequivalence Study of Generic GPO Saquinavir and Norvir® Versus Invirase® and Norvir®

Study Overview
=================
Brief Summary
-----------------
The previous two studies of generic GPO saquinavir failed to prove bioequivalence. In this study the bio-equivalence will be investigated in healthy Thai volunteers, to see whether the generic GPO saquinavir shows bioequivalence when boosted with Norvir®. If the generic formulation is bioequivalent subsequent studies may follow in HIV-1 positive patients.

Detailed Description
-----------------
The primary objective is to establish bioequivalence of ritonavir boosted generic GPO saquinavir, with Invirase® and Norvir® as the reference drug. The secondary objective is to evaluate the short-term tolerability and safety profiles of generic saquinavir in healthy male volunteers.

Official Title
-----------------
Bioequivalence Study of Generic GPO Saquinavir and Norvir® Versus Invirase® and Norvir® in Thai Healthy Volunteers

Conditions
-----------------
HIV Infections

Intervention / Treatment
-----------------
* Drug: generic GPO saquinavir and novir vs invirase and norvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Healthy male 18-45 years old Documented negative test for HIV-1 infection < 1 wk prior to start of study and with no risk of HIV exposure in the last 6 months BMI 18-25 Normal physical examination Normal CBC, BUN, Cr, AST, ALT, Total bilirubin, no evidence of active or chronic HBV or HCV infection Exclusion Criteria: History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the study. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion. Inability to understand the nature and extent of the study and the procedures required. Participation in a drug study within 60 days prior to the first dose. Febrile illness within 3 days before the first dose. Use of concomitant medication Smoke cigarettes not more than 10 cigarettes a day. Drink alcohol not more than 2 units a day. Discontinue smoking and alcohol for at least 1 month before enrollment. Take other medication regularly Involvement in any drug addiction. Heart disease, hypertension, liver disease, kidney disease, GI disease, allergic disease or other diseases which may interfere with the PK of study drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Day 1: receive a single dose of Invirase®/Norvir® 1,000 mg / 100mg 7-day washout period will follow. Day 8: take generic GPO squinavir/Norvir | Drug: generic GPO saquinavir and novir vs invirase and norvir<br>* Norvir® 100mg capsules, Invirase® 1,000 mg capsules Generic GPO Saquinavir 1,000 mg capsules For phase 1 and 2 - At day 1 subjects of group A will receive a single dose of Invirase®/Norvir® 1,000 mg / 100mg, while group B will receive generic GPO saquinavir / Norvir® 1,000 mg / 100mg as single dose. The same day the first 24 hr PK curve will be done. After this, a 7-day washout period will follow. At day 8 group A will take generic GPO saquinavir / Norvir® and Group B will take Invirase®/Norvir®. At this day, the second 24 hr PK curve will be done<br>|
| Active Comparator: B<br>Day 1: take generic GPO squinavir/Norvir 7-day washout period will follow. Day 8: receive a single dose of Invirase®/Norvir® 1,000 mg / 100mg | Drug: generic GPO saquinavir and novir vs invirase and norvir<br>* Norvir® 100mg capsules, Invirase® 1,000 mg capsules Generic GPO Saquinavir 1,000 mg capsules For phase 1 and 2 - At day 1 subjects of group A will receive a single dose of Invirase®/Norvir® 1,000 mg / 100mg, while group B will receive generic GPO saquinavir / Norvir® 1,000 mg / 100mg as single dose. The same day the first 24 hr PK curve will be done. After this, a 7-day washout period will follow. At day 8 group A will take generic GPO saquinavir / Norvir® and Group B will take Invirase®/Norvir®. At this day, the second 24 hr PK curve will be done<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish bioequivalence of ritonavir boosted generic GPO saquinavir generic, with Invirase® and Norvir® as reference drug. |  | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary objective is to evaluate the short-term tolerability and safety profiles of generic saquinavir in healthy male volunteers. |  | 8 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bioequivalence, ritonavir boosted generic GPO saquinavir, saftey, pharmacokinetics