Bioequivalence study of atorvastatin 40 mg film coated tablet produced by PT Pratapa Nirmala in comparison with the comparator drug (Lipitor® 40 mg Film Coated Tablet manufactured by Pfizer Pharmaceuticals LLC Vega Baja Puerto Rico, USA; packed and released by Pfizer manufacturing Deutschland GmbH, Germany; imported by PT Pfizer Indonesia) when administered under fasting condition in healthy subjects

1. Background
Registration Number	INA-NZAXLYO
Date of registry approval	14-11-2023
Registration Date	30-10-2023
Secondary identifiers	Yes
Name of issuing authority (for example protocol number, other registries, etc)	BPOM
Secondary identifier number	BE. 740/EQL/2022
Scientific study title	Bioequivalence study of atorvastatin 40 mg film coated tablet produced by PT Pratapa Nirmala in comparison with the comparator drug (Lipitor® 40 mg Film Coated Tablet manufactured by Pfizer Pharmaceuticals LLC Vega Baja Puerto Rico, USA; packed and released by Pfizer manufacturing Deutschland GmbH, Germany; imported by PT Pfizer Indonesia) when administered under fasting condition in healthy subjects
Public (popular study title)	Bioequivalence study of atorvastatin 40 mg film coated tablet produced by PT Pratapa Nirmala in comparison with the comparator drug (Lipitor® 40 mg Film Coated Tablet manufactured by Pfizer Pharmaceuticals LLC Vega Baja Puerto Rico, USA; packed and released by Pfizer manufacturing Deutschland GmbH, Germany; imported by PT Pfizer Indonesia) when administered under fasting condition in healthy subjects

2. Sponsor and Funding
Primary Sponsor	PT Pratapa Nirmala
Source(s) of monetary or material support	PT Pratapa Nirmala
Other partners	PT Equilab International

3. Contact details
Principal Investigator
Principal investigator	dr. Danang Agung Yunaidi
City	Jakarta
Country	Indonesia
Principal investigator's affiliation	PT Equilab International
Principal Investigator's email address	danang@equilab-int.com
Public Queries
Contact person name for public queries	Ronal Simanjuntak
Address for public queries	PT Equilab International, Jl. RS. Fatmawati Persil 33
City	Jakarta
Country	Indonesia
ZIP	12430
Affiliation for public queries	PT Equilab International
Email address for public queries	info@equilab-int.com
Phone number for public queries	+62 21 7695513, 7515932
Scientific Queries
Name of Contact for scientific queries	dr Danang Agung Yunaidi
Address for scientific queries	PT Equilab International, Jl. RS. Fatmawati Persil 33
City	Jakarta
Country	Indonesia
ZIP	12430
Affiliation of scientific queries contact	PT Equilab International
Email address for scientific queries	danang@equilab-int.com

4. IRB & Regulatory
Ethical Approval number	No. KET-1324/UN2.F1/ETIK/PPM.00.02/2022
Name of Ethics committee	Komite Etik Penelitian Kesehatan Fakultas Kedokteran Universitas Indonesia - RSUPN Dr. Cipto Mangunkusumo
Date of Ethic approval	05-12-2022
Contact details of Ethic Committee (phone, email, and office)	Jl. Salemba 6, Jakarta Pusat; Whatsapp: 0856-8701-608; Telp. 021 315 7008; e-Mail: ec_fkui@yahoo.com
Number of Persetujuan Pelaksanaan Uji Klinik (PPUK)/Persetujuan Protokol Uji BE (PPUB)	RG.01.02.321.02.23.01541/UB

5. Status
Countries of recruitment	Indonesia
Study sites in Indonesia	PT Equilab International
Recruitment status	Complete
Date of first enrollment	20-03-2023
Targeted Sample size	00030 -
Number of enrolled participants	30
Date of study completion (last participant, last visit)	29-03-2023

6. Study Design & Purpose
Primary health condition(s) or problem(s) studied (e.g., depression, breast cancer,medication error)	Healthy human subjects
Purpose of the study	Bioeequivalence study
Study type	Interventional
Interventional Study category	Bioequivalence study
Method of allocation
Description of the allocation concealment mechanism and sequence generation
Masking
Study intervention (study arm)	one atorvastatin 40 mg film coated tablet of test drug (T) given as a single oral dose with 250 mL of water at ambient temperature after an overnight fast of at least 10 hours
Control intervention (control arm)	one of Lipitor® 40 mg Film Coated Tablet of comparator drug (R) given as a single oral dose with 250 mL of water at ambient temperature after an overnight fast of at least 10 hours
Intervention assignment	Crossover

7. Eligibility Criteria
Gender inclusion criteria	Male, Female
Minimum age	18
Maximum age	55
Inclusion criteria	Able to participate, communicate well with the investigators and willing to provide written informed consent to participate in the study; Healthy male and female subjects with absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during the screening and could be considered healthy based on the evaluation; Aged 18-55 years inclusive; Non-smokers; Body mass index within 18 to 25 kg/m2; Vital signs (after 10 minutes rest) must be within the ranges (Systolic blood pressure : 100 – 129 mmHg; Diastolic blood pressure : 60 – 84 mmHg; Pulse rate : 60 – 90 bpm; Respiratory rate : 12-20x / minutes; Body temperature : < 37.5°C); Willing to practice abstention or non-hormonal contraception during the study.
Exclusion criteria	History of allergy or hypersensitivity or contraindication to atorvastatin or allied drug; Pregnant or lactating female (urinary pregnancy test will be applied to female subjects at screening and before taking the study drug); Any major illness in the past 90 days or clinically significant ongoing chronic medical illness; Presence of any clinically significant abnormal values during screening e.g. significant abnormality of liver function test (AST, ALT, alkaline phosphatase, total bilirubin, direct bilirubin ≥ 1.5 ULN), renal function test (serum creatinine concentration > 1.4 mg/dL and ureum ≥ 1.5 ULN), etc; Positive Hepatitis B surface antigen (HBsAg), anti-HCV, or anti-HIV; Positive result for COVID-19 rapid antigen test (this criteria will only be applied if the study conduct during pandemic condition); Clinically significant hematology abnormalities; Clinically significant electrocardiogram (ECG) abnormalities; Any surgical or medical condition (present or history) which might significantly alter the absorption, distribution, metabolism or excretion of the study drug, e.g. gastrointestinal disease including gastric or duodenal ulcers or history of gastric surgery; Past history of anaphylaxis or angioedema; History of drug or alcohol abuse within 12 months prior to screening for this study; Participation in any clinical trial within the past 90 days calculated from the last visit until this study’s first dosing day; History of any bleeding or coagulative disorders; Presence of difficulty in accessibility of veins in left or right arm; A donation or significant blood loss within 90 days before this study’s first dosing day; Intake of any prescription (especially atorvastatin), non-prescription drug (including hormonal contraception), food supplements or herbal medicines within 21 days of this study’s first dosing day.

8. Study Outcome
Primary Outcome
Name of primary outcome	AUC0-t dan Cmax
Metric/method of measurement	The plasma concentrations of atorvastatin were determined by using validated ultra performance liquid chromatography with tandem mass spectroscopy detection (UPLC MS/MS) method
Timepoint(s) of measurement	Blood samples were drawn before taking the drug, and at 0.17, 0.33, 0.50, 0.75, 1.00, 1.50, 2.00, 2.50, 3.00, 4.00, 6.00, 9.00, 12.00, 16.00, 24.00, 36.00, and 48.00 hours after drug administration

9. Study Results
Brief summary of study results	it was concluded that atorvastatin 40 mg film coated tablet produced by PT Pratapa Nirmala were bioequivalent to the comparator drug (Lipitor® 40 mg Film Coated Tablet manufactured by Pfizer Pharmaceuticals LLC Vega Baja Puerto Rico, USA; packed and released by Pfizer manufacturing Deutschland GmbH, Germany; imported by PT Pfizer Indonesia)
Date of results summaries	16-05-2023
Participant flow	30 subjects enrolled and completed
Baseline characteristic
Adverse events	No adverse event during study
Outcome measures	90% confidence interval

10. Publication
URL hyperlink(s) related to results and publications
IPD sharing statement (Statement regarding the intended sharing of deidentified individual clinical trial participant-level data (IPD))	No
Plan for IPD sharing (what IPD will be shared, when, by what mechanism, with whom, and for what types of analyses)
Other important informations	NA