.

Bioequivalence Study 25 mg Quetiapine FC Tablets (Quetvell®)

Produced by PT. Novell Pharmaceutical Laboratories
in Comparison With Seroquel® 25 mg FC Tablets
(AstraZeneca UK Limited)

(Study Number: LV/72/CL/2011)

A Bioequivalence Study Conducted by:

PT. Clinisindo Laboratories

Sponsored by:
PT. Novell Pharmaceutical Laboratories

Jakarta, December 2012

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Study Title
Bioequivalence Study 25 mg Quetiapine FC Tablets (Quetvell®) Produced by PT. Novell
Pharmaceutical Laboratories in Comparison With Seroquel® 25 mg FC Tablets
(AstraZeneca UK Limited)

Protocol Number
LV/72/CL/2011 version 2

Sponsor
Name : PT. Novell Pharmaceutical Laboratories.
Address : Jl. Pos Pengumben No. 8, Sukabumi Selatan, Kebon Jeruk
Jakarta 11560, Indonesia
Phone (62-21) 5355 888, Fax. (62-21) 5355 822

Study Site
Clinical Facility, Analytical Laboratory, Pharmacokinetic and Statistic Institution
Name : PT. Clinisindo Laboratories
Address : Jl. Ulujami Raya No.12, Pesanggrahan
Jakarta Selatan 1220.25, Indonesia
Phone (62-21) 7388 9918, Fax (62-21) 7388 5453

Clinical Analysis Laboratory

Name : Laboratorium Klinik Prodia
Address : Jl. Gunawarman No. 77
Kebayoran Baru
Jakarta Selatan 12180, Indonesia
Phone (62-21) 722 0203

Phase Study
I Bioequivalence Study

Study Period
October-December 2012
Dosing : Phase I, October 10th, 2012 at 07.00 am
Phase II, October 17 th, 2012 at 07.00 am
Blood sampling : Phase I, October 10th -11th, 2012
Phase II, October 17th -18th, 2012
Drug analysis : October 19th - 30th, 2012

Principal and Coordinating Investigators

Principal Investigator : Prof. Dr. Yahdiana Harahap, MS, Apt.
Sub Investigator : Budi Prasaja, S.Si., MM, Apt.
Windy Lusthom, S.Si., Apt.
Lia Yumi Yusvita, S.Farm., Apt.
Theresia Sinandang, S.Farm, Apt.
Vita Felicia, S Farm, Apt.
Responsible doctor : dr. Lianna Y. Panjaitan

“ This study has been performed according to the protocol and

was performed in compliance with Good Clinical Practice.”

Warning Confidentially
No section of the present document will be disclosed to any third party without written permission
QUALITY from PT ASSURANCE
Novell PharmaceuticalSTATEMENT
Laboratories

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)

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QUALITY ASSURANCE STATEMENT

Study Number : LV/72/CL/2011

Study Title : Bioequivalence Study 25 mg Quetiapine FC Tablets (Quetvell®)

Produced by PT. Novell Pharmaceutical Laboratories in
Comparison With Seroquel® 25 mg FC Tablets (AstraZeneca
UK Limited)

Principal Investigator : Prof. Dr. Yahdiana Harahap, MS, Apt

In compliance with the principles of Good Laboratory Practice (GLP), Good Clinical
Practice (GCP), protocol and relevant Standard Operating Procedure (SOP) this study
has been inspected. This final report audited by Quality Assurance in PT. Clinisindo
Laboratories.

This report describes the methods and procedures used in the study and the results
incorporated in this report accurately reflect the raw data of this study.

Hardiyanti, S.Si, Apt _______________________

Quality Assurance Date :

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)

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INVESTIGATORS SIGNATURES

Study Number : LV/72/CL/2011

Study Title : Bioequivalence Study 25 mg Quetiapine FC Tablets

(Quetvell®) Produced by PT. Novell Pharmaceutical
Laboratories in Comparison With Seroquel® 25 mg FC
Tablets (AstraZeneca UK Limited)

“I have read this report and confirm that to the best of my knowledge it accurately
describes the conduct and results of the study”

Prof. Dr. Yahdiana Harahap, MS, Apt. _______________________

Principal Invesigator Date :

Budi Prasa S.Si, MM, Apt.

Sub investigator Date :

Windy Lusthom, S.Si, Apt.

Sub investigator Date :

Mena Bertony Ginting, S.Si, Apt.

Sub investigator Date :

Vita Felicia, S.Farm, Apt.

Sub investigator Date :

dr. Lipin
Responsible doctor Date :

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)

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2. SYNOPSIS

Name of Sponsor :
PT. Novell Pharmaceutical Laboratories
Name of Finished Product:
Quetvell® 25 mg FC Tablet
Name of Active Ingredient:
Quetiapine Fumarate

Study Number:
LV/72/CL/2011

Title of Study:
Bioequivalence Study 25 mg Quetiapine FC Tablets (Quetvell®) Produced by PT. Novell
Pharmaceutical Laboratories in Comparison With Seroquel® 25 mg FC Tablets (AstraZeneca
UK Limited)

Objective:
The aim of this study is to assess the bioequivalence of 25 mg Quetiapine FC Tablets
(Quetvell®) Produced by PT. Novell Pharmaceutical Laboratories, compared to the reference
product Seroquel® 25 mg FC Tablets (AstraZeneca UK Limited)

Phase of Development:
I Bioequivalence Study

Studied Period:
Date of first enrollment:
October 10th, 2012
Date of last completed:
October 18th, 2012

Study Design:
This study was conducted in randomized two-way crossover design with one-week wash-out
period under fasting conditions.

Investigators:
Yahdiana Harahap, Budi Prasaja, Windy Lusthom, Theresia Sinandang, Lia Yumi Yusvita,
Vita Felicia, dr. Lianna Y. Panjaitan

Study Centre:
PT. Clinisindo Laboratories, Jl.Ulujami Raya No. 12, Pesanggrahan, Jakarta-Indonesia 12250
Ph. (62 21) 7388 9918, Fax. (62 21) 7388 5453

Test product, dose and mode administration, batch number:

Quetvell® 25 mg FC Tablets, a single dose, oral administration, batch no.: 12M271

Reference product, dose and mode administration, batch number:

Seroquel® 25 mg FC Tablets, a single dose, oral administration, batch no.: JB237

Treatment:
Subjects were fasted 10 hours before each drug administration. Each subject received
one FC tablet of quetiapine with 240 ml of water. Serial blood samples were collected at the
following time points: before dosing, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24
hours after drug administration and was repeated after one-week wash-out period. Meals were
standardized and were provided similar in both sampling periods.

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)

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Name of Sponsor :
PT. Novell Pharmaceutical Laboratories
Name of Finished Product:
Quetvell® 25 mg FC Tablet
Name of Active Ingredient:
Quetiapine Fumarate

Statistical Method:
Descriptive statistics (mean, median, standard deviation, minimum and maximum) were
calculated to AUC0-t, AUC0-∞, Cmax, tmax, and t½. Analysis of variance (ANOVA) was performed
using logarithmically transformed AUC0-t, AUC0-∞ Cmax, and t½..
Bioequivalence was to be concluded if the parametric 90% confidence intervals were within
limits of 80.00-125.00%.
Tmax was analyzed by nonparametric method (Wilcoxon sign rank test).

Criteria for evaluation:

Pharmacokinetic
The following pharmacokinetic parameters were calculated from the concentration-time profiles
of quetiapine following oral administration: area under the plasma concentration versus time
curve from time zero to the time point with the last measurable concentration (AUC0-t),
extrapolated area under the plasma conocentration versus time curve from time zero to infinity
(AUC0-∞), maximum observed plasma concentration (Cmax). Time to reach Cmax (tmax) and
terminal elimination half-life (t½) were also calculated as additional evaluation.
The concentration of quetiapine in plasma will be determined using LC-MS/MS method with
TurboIonSpray (electrospray) ionization mode.
Safety
Adverse events and serious adverse events were recorded during the study.

Study Population:
Healthy subjects, both sexes, age between 18 to 47 years old, body weight with normal range,
acceptable medical history and physical examination, negative result for pregnancy test and
serological tests of Hepatitis B, Hepatitis C, and HIV, acceptable clinical laboratory tests
including renal function, liver function, routine blood, urine analysis and ECG.

Number of Subjects:
Screened N 27
Enrolled & Randomised N 26
Completed N 24
Total number subjects discontinued N 2
Withdrawn n 0
Withdrew consent n 2
Safety population N 24
Pharmacokinetic population N 24
Demographics:
N (all subjects evaluated) 24
Females: Males 5 : 19
Mean age in years (SD) 30.7 (8.0)
Mean weight in kg (SD) 56.5 (8.2)
Mean height in cm (SD) 163.6 (6.6)
Race, n (%) Not applicable

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)

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Name of Sponsor :
PT. Novell Pharmaceutical Laboratories
Name of Finished Product:
Quetvell® 25 mg FC Tablet
Name of Active Ingredient:
Quetiapine Fumarate

Summary-Conclusion

Efficacy Results
Test Reference T/R Point Confidence
Parameter
Formulation Formulation Estimate Limits
C max (ng/mL)
Geometric mean 71.53 75.03 95.34 83.23 – 109.20
Range 21.26 – 168.60 28.43 – 161.50
AUC0-t (ngxh/ml)
Geometric mean 266.94 298.27 89.50 80.39 – 99.64
Range 103.03 – 559.60 183.32 – 516.70
AUC0-∞ (ngxh/ml)
Geometric mean 272.09 304.46 89.37 80.26 – 99.51
Range 105.29 – 599.48 186.26 – 553.42
t1/2 (h)
Geometric mean 3.69 3.93 93.90 90.70 – 97.21
range 5.99 – 23.54 2.57 – 7.89
tmax (h)
Median 0.75 0.75 Not applicable Not applicable
range 0.50 – 2.00 0.50 – 2.50
Safety Results

Period I Period II

N (all subjects dosed) 24 24

Adverse Events:
Number of subject with AEs n (%) 23 (95.8) 23 (95.8)
Most of frequent AEs (n≥2) (%)
Somnolence 19 (79.2) 21 (87.5)
Dizziness 8 (33.3) 6 (25)
Dry Mouth 7 (29.2) 14 (58.3)
Nausea 3 (12.5) 0 (0)
Weakness 2 (8.3) 0 (0)
Polyuria 0 (0) 5 (20.8)

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)

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Name of Sponsor :
PT. Novell Pharmaceutical Laboratories
Name of Finished Product:
Quetvell® 25 mg FC Tablet
Name of Active Ingredient:
Quetiapine Fumarate

Conclusion:
Based on these results, we conclude that both formulations are bioequivalent.

Publications:
None of publication at the date of report.

Date of the Report: December 11th, 2012

Study Number: LV/72/CL/2011 (Date of report: December 11th, 2012)