A Fully Replicate, Cross-over, Bioequivalence Study to Compare Two Prolonged Release, Multi-matrix Tablet Formulations of Budesonide in Healthy Indian Adults
Published: April 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/60894.17660
Ankith Rai, Kushal Sarda, Lokesh Yadav, Anadya Prakash Tripapathi, Sachin Joshi, Rajan Verma, Manisha Patil, Nilesh Lad
1. Head-Clinical Development and Operations, Department of Established Pharmaceuticals Division, Abbott Healthcare Pvt. Ltd., Mumbai, Maharashtra, India.
2. Head-Medical Affairs, Department of Established Pharmaceuticals Division, Abbott India Ltd., Mumbai, Maharashtra, India.
3. Senior Manager-Clinical Pharmacology/Pharmacokinetics, Department of Established Pharmaceuticals Division, Abbott Healthcare Pvt. Ltd., Mumbai, Maharashtra, India.
4. Senior Manager-Principal Biostatistician, Department of Established Pharmaceuticals Division, Abbott Healthcare Pvt. Ltd., Mumbai, Maharashtra, India.
5. Clinical Project Lead, Department of Established Pharmaceuticals Division, Abbott India Ltd., Mumbai, Maharashtra, India.
6. Director-Formulation Development, Department of Established Pharmaceuticals Division, Abbott Healthcare Pvt. Ltd., Mumbai, Maharashtra, India.
7. Associate Director-Formulation Research and Development, Department of Established Pharmaceuticals Division, Abbott Healt
Correspondence
Dr. Ankith Rai,
Godrej BKC, Plot No. C-68, Bandra, Kurla Complex, Near MCA Club, Bandra (E), Mumbai, Maharashtra, India.
E-mail: ankith.rai@abbott.com
Introduction: Budesonide is a synthetic, non halogenated corticosteroid, structurally related to 16α-hydroxyprednisolone, which is approved as first-line therapy for various gastrointestinal disorders. Budesonide prolonged-release tablets incorporating multi-matrix technology {Cortiment® 9 mg: Reference product (R)} were approved in India for induction of remission in adult patients with mild-to-moderate active ulcerative colitis.
Aim: To assess the bioavailability, safety and tolerability of a single dose of generic budesonide prolonged-release tablets 9 mg {CortirowaTM OD; Test product (T)} and demonstrate their bioequivalence to Reference product (R) in healthy Indian adults under fasting conditions.
Materials and Methods: In this randomised, open-label, single-dose, balanced, 2-treatment, 2-sequence, 4-period, fully replicate, cross-over bioequivalence study was conducted from 12th July 2021 to 8th August 2021 at Ecron Acunova Limited, Manipal, India. Total 56 participants were randomly allocated (1:1) to treatment sequences Test-Reference-Test-Reference (TRTR) or Reference-Test-Reference-Test (RTRT). After a 10-hour overnight fasting, participants were administered a single oral dose of T or R along with 240 mL of water. After each dose, a total of 26 venous blood samples (each 4 mL) were collected from each participant, at hourly intervals until 20 hours, and at 24, 30, 36, 48, and 72 hours. Plasma budesonide concentrations were analysed using a validated Liquid Chromatography-Tandem-Mass Spectrometry (LC-MS/MS) method. Based on the randomisation sequences, the treatment periods were defined as test product treatment Period-1 (T1), test product treatment Period-2 (T2), reference product treatment Period-1 (R1), and reference product treatment Period-2 (R2). The primary pharmacokinetic parameters were peak plasma concentration (Cmax) and area under the concentration-time curve from time zero to the last sample with quantifiable concentration (AUC0-t).
Results: Test and reference products were comparable in terms of mean (standard deviation) Cmax {pg/mL: T1=2163.0 (1423.9) and T2=2456.25 (1346.035) vs R1=2301.59 (1582.995) and R2=2437.62 (1437.665)} and AUC0-t {hr.pg/mL: T1=27938.0 (16431.23) and T2=33629.58 (18407.253) vs R1=25882.41 (17250.267) and R2=33146.25 (19350.222)}. As the within-subject Standard Deviation (SD) of R (SWR) for Cmax and AUC0-t was ≥0.294, the reference-Scaled Average Bioequivalence (SABE) approach was used. The bioequivalence criteria prespecified using the Scaled Average Bioequivalence (SABE) approach was met as the 95% upper confidence bound for (μT-μR)2- θs2WR of Cmax (-0.255371831) and AUC0-t (-0.445865013) were both ≤0, and the point estimate (T/R) geometric mean ratio of Cmax (0.97) and AUC0-t (1.06) were both within 0.80 and 1.25. While 10 Adverse Events (AEs) were reported in the study, all were of mild intensity.
Conclusion: CortirowaTM OD was bioequivalent to Cortiment® 9 mg in healthy Indian adults under fasting conditions. Both the products were found to be well-tolerated.
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