CTRI/2015/06/005929 [Registered on: 18/06/2015] Trial Registered Prospectively
Last Modified On:
27/11/2015
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study comparing Nevirapine Extended Release Tablet 400 mg of Apotex Inc. and Viramune® XR Extended-Release Tablet 400 mg of Boehringer Ingelheim Pty Limited., Australia in Patients Under Fasting Conditions in adult HIV-1 Infected patients stabilized on Nevirapine
Scientific Title of Study
An Open-Label, Randomized, Two-Treatment, Two Period, Two Sequence, Crossover, Multicentre, Multiple Dose, Steady State Bioequivalence study of Nevirapine Extended Release Tablet 400 mg of Apotex Inc. and Viramune® XR Extended-Release Tablet 400 mg of Boehringer Ingelheim Pty Limited., Australia in Patients Under Fasting Conditions.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CRL111428, Version 1.0 dated 20 Dec 2014
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
First Floor, Department of Medicine,Shri Pramukhswami maharaj marg, Adjan Char Rasta, Adajan,
Surat-395009, Gujarat, India.
Surat GUJARAT
09825312027
bapsclinicalresearch@gmail.com
Dr John Thomas Ramapuram
Kasturba Medical College Hospital
Department of General
Medicine-II, 1st floor,Attavar, Mangalore-575 001, Karnataka, India Uttara Kannada KARNATAKA
08242425092
john@ramapuram.net
Dr Jai Prakash Kawlani
Mavens Hospital
Department of
Medicine, Ground
Floor,N-37, Vaishali Nagar, Ajmer, Rajasthan- 305 001, India Ajmer RAJASTHAN
7737651589
drjaiprakashkewalani@gmail.com
Dr Keyur Shah
Medilink Hospital,
Department of
Medicine, 1st Floor
Medilink Hospital
Nr. Shyamal Cross Road, 132 Ft. Ring Road, Satellite, Ahmedabad- 380 015, Gujarat, India Ahmadabad GUJARAT
9879004822
drkeyurshah@yahoo.com
Dr Srinivasa M
Mysore Medical College
Department of General
Medicine,
Ground floor
Administrative Block,
Irwin Road,
Mysore-570001,
Karnataka, India
Mysore
KARNATAKA Mysore KARNATAKA
08212420142
drsrinivasam@gmail.com
Dr Rajiv Ranjan Dutta
Paras Hospitals
Department of Medicine,C-1 Block, Sushant Lok- Phase –I, Sector-43, Gurgaon, Haryana-122 002, India Gurgaon HARYANA
9811742549
rrduttas@gmail.com
Dr Prakash Kurmi
Shivam Hospital & Diagnostic Centre,
Groumd Floor, Director cabin,C/4 Satyanarayan Society, Gor’s Kuva, Near JashodanagarCross Road, Maninagar, East, Ahmedabad- 380 008 Ahmadabad GUJARAT
9825047692
dr_prakashkurmi@yahoo.co.in
Dr M N Lakshmikanth Reddy
Surakshaka Diabetic Centre Pvt. Ltd.,
Department of General
Medicine, OPD-I,
Ground floor
MIG- 218, KPHB Main Road, Kukatpally, Hayderabad- 500 072, AP, India Hyderabad ANDHRA PRADESH
04040061930
mnlkreddy@gmail.com
Dr Alap Mehta
Unique hospital multispeciality & Research Institute
Department of
Medicine, Ground
Floor,Opp. Kiran Motor, Nr. Cana, Civil Hospital Char Rasta- Sosyo Circle Lane, Off. Ring Road, Surat- 395 002, Gujarat, India Surat GUJARAT
Ethics Committee, BAPS Pramukh Swami Hospital, Adajan Cross Road, Nr. Country Club, Adajan, Surat- 395 009, Gujarat, India
Approved
Ethics Committee, Medilink Institutional Ethics Committee, Basement Medilink Hospital, Nr. Shyamal Cross Road, 132 Ft. Ring Road, Satellite, Ahmedabad- 380 015, Gujarat, India
Approved
Ethics Committee, Unique hospital,- multispeciality & Research Institute, Opp. Kiran Motor, Nr. Cana, Civil Hospital Char Rasta- Sosyo Circle Lane, Off. Ring Road, Surat- 395 002, Gujarat, India
Not Applicable
Institutional Ethics Committee Paras Hospital C-I, Sushant Lok , Phase- I,Sector-43 Gurgaon-122 002, India
Not Applicable
Institutional Ethics committee, Mysore Medical college and Research Institute and Associated Hospitals, Mysore
Approved
Manipal University Ethics Committee, 7th Floor, Kasturba Hospital, Attavar, Magalore-575 001, Karnataka, India
Approved
Mavens Institutional Ethics Committee, 1st Floor, Mavens, N-37, Lane Opposite Reliance Fresh, Vaishali Nagar, Ajmer-305 001, Rajasthan, India
Nevirapine Extended Release Tablet 400 mg of Apotex Inc..
Oral, Once daily for 11 Days
Comparator Agent
Viramune® XR
Viramune® XR Extended-Release Tablet 400 mg of Boehringer Ingelheim Pty Limited., Australia,
Oral, Once daily for 11 Days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
Subjects participating in the study must have:
1. Able to understand and willing to sign the informed consent form
2. Male and Non pregnant, non-lactating female subjects 18-65 years of age with documented HIV-I infection
3. BMI 18-30 kg/m2
4. Already receiving stable Nevirapine based regimen at least since 12 weeks either immediate release or extended release in combination with:
a. Zidovudine and Lamivudine or
b. Tenofovir and Lamivudine as separately prescribed components and to be kept constant throughout the study
5. An HIV viral load < 50 copies/mL at screening
6. A CD4+ T cell count > 50 cell/mm3
7. Willingness of study participants to comply with the all the study requirements
8. Willingness of study participants to not plan a child during the study
Clinically acceptable screening laboratory values that indicate adequate baseline organ function
ExclusionCriteria
Details
1. History of allergy or hypersensitivity reactions to Nevirapine or the ingredients of the formulation
2. Current treatment with an HIV protease inhibitor
3. Clinically significant cardiac, liver or kidney disease
4. Having moderate to severe renal dysfunction or serum creatinine > 3 X ULN
5. Females who are pregnant or breast feeding or planning to become pregnant or subjects not willing to take appropriate measures to prevent pregnancy during the study
6. ALT or AST ≥ 3 X ULN, Bilirubin > 2 X ULN
7. Any contraindication to use of Nevirapine
8. Past history or currently suffering from tuberculosis
9. Relevant history or current condition, illness that might interfere with drug absorption, distribution, metabolism or excretion
10. Use of concomitant medication (other than the stable background antiretroviral HIV therapy) that may interfere with the pharmacokinetics of Nevirapine and/or the background antiretroviral HIV therapy
11. Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days of drug administration.
12. Use of enzyme-modifying drugs within 30 days prior to receiving the first dose of study medication (listed in Appendix-II). They can be allowed depending on Principal Investigator’s discretion in consultation with Medical monitor, if they are kept constant in the last 30 days and are expected to remain constant during the study period.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Cmax,ss, AUCtau, Tmax,ss, Cmin,ss, Cav,ss, Ctauss and % Fluctuation for Nevirapine
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20 and 24 hours post
dose.
Secondary Outcome
Outcome
TimePoints
NIL
NIL
Target Sample Size
Total Sample Size="30" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The sponsor has developed the test formulation. This study is being conducted to compare the bioavailability and characterize the Pharmacokinetic profile of the sponsor’s
formulatons (Nevirapine Extended Release 400 mg tablets) with reference formulation (Viramune® XR Extended Release 400 mg tablets) in HIV-I Infected patients under fasting conditions, stabilized on Nevirapine based regimen either immediate release or prolonged release to assess the bioequivalence. The most adverse reactions associated with nevirapine are rash, fever, nausea,headache, fatigue, somnolence, vomiting, diarrhoea, abdominal pain and myalgia. Cases of anaemia and neutropenia may be associated with VIRAMUNE therapy. Arthralgia has been reported as a stand-alone event in rare instances in patients receiving VIRAMUNE containing regimens. etc., regulatory authorities are recommending that studies should be conducted on HIV-I infected patients.
Since the formaulation being studied is a extended release formaulation, a multiple dose, stady state study is being conducted as per applicable regulatory guidance. The study is being conducted on patients who are on a stable dose of Nevirapine based regimen, and the patient cannot be deprived of the Nevirapine treatment during the washout period of the study. Hence, the study has been planned to be a continuous administration of the test and reference formulation without any intervening washout period.
Objective: To evaluate the pharmacokinetic bioequivalence of the test and reference products and to monitor safety of the patients. The total number of patients to enroll is around 30 from India.