A pharmacoscintigraphy study to observe the disintegration pattern and gastric emptying pattern of etoricoxib 60mg + paracetamol 325mg oral tablet marketed by Systopic laboratories private limited in 12 healthy adult human subjects

Protocol Title:

A pharmacoscintigraphy study to observe the disintegration pattern and gastric emptying pattern of Etoricoxib 60mg + Paracetamol 325mg oral tablet marketed by Systopic Laboratories Private Limited in 12 healthy adult human subjects.

|Objectives:

Primary Objective

·       To evaluate the disintegration pattern and gastric emptying pattern of Etoricoxib 60mg + Paracetamol 325mg oral tablet marketed by Systopic Laboratories Private Limited.

Secondary Objective

·       To monitor the safety of the subjects.

|Study Design:

An open label, single arm, single dose, single-period, single-treatment, single-sequence, oral pharmacoscintigraphy based clinical study.

|No. of subjects**:**

A sufficient number of subjects will be enrolled to ensure dosing of 12 healthy adult human subjects.

|Housing:

At least 2 hours prior to dosing until at least 12 hours post dose

|Study duration**:**

Considering the minimum washout period, expected study duration of clinical part is 8 days from the day of check-in.

|Investigational Product

Product

Etoricoxib 60mg + Paracetamol 325mg tablet

|Dosage Form

Tablet

|Strength

60 mg/325 mg

|Drug Name

Etoricoxib (60 mg) and Paracetamol (325 mg)

|Manufactured By

Systopic Laboratories Private Limited

|Radioactive Element

Technetium Pertechnetate - 99mTcO4

|Radiation Dose

99mTc- labelled - -- will contain 100-150 µCi of Technetium pertechnetate/ Tablet.

|Inclusion Criteria

i.    Subject who are able to understand and ready to provide written informed consent.

ii.    Subject must be healthy male human beings within 18-45 years of age (both inclusive).

iii.    Subject should be having Body Mass Index (BMI) in the range 18.5-30 kg/m2 and weighing at least 50 kg.

iv.    Subject must be of normal health as determined by medical history and physical examination, and laboratory tests performed within 21 days prior to the commencement of the study.

v.    Subject whose screening laboratory values are within normal limits or considered by the physician / Principal Investigator to be of no clinical significance.

|Exclusion Criteria

i.     Subject incapable of understanding the informed consent process or not ready to sign informed consent.

ii.     Subject with significant history of hypersensitivity to Study Drug or any ingredients of the formulation or any related products as well as severe hypersensitivity reactions (like angioedema) to any drugs.

iii.     Subject with of presence or history of significant gastrointestinal, liver or kidney disease, or any conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects.

iv.     Subject with active peptic ulceration or a history of peptic ulceration.

v.     Subject with resting hypotension (BP <90 /60) or hypertension (BP > 139 /89).

vi.     Subject with Pulse rate below 50/ min. and above 99/min.

vii.     Subjects with or prior history of clinically significant, Cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, musculoskeletal, neurological or psychiatric disease.

viii.     Investigations with urine samples of subject’s shows clinically abnormal chemical and microscopic examination of urine defined as presence of RBC, WBC, >4HPF, Glucose (Positive) or Protein (Positive).

ix.     Subjects with a history of MI, Stroke, Peripheral Arterial Disease, GI Bleeding, Hepatic Impairment, Renal Impairment, Epilepsy and Intracranial hemorrhage.

x.     Subject has inability to communicate well (i.e. language problem, poor mental development, psychiatric illness or poor cerebral function) that may impair the ability to provide, written informed consent.

xi.   Subject with a history of known food allergy.

xii.   Subject who has suffered any illness or who has been hospitalized within the last 4 weeks preceding the start of the study.

xiii.   Subject who has taken over the counter or prescribed medications, including any enzyme modifying drugs within the last 14 days prior to the study.

xiv.   Subject with a history of drug abuse or alcoholism i.e. alcohol consumption > 2 units / day or 10 units / week (one unit of alcohol = 50 ml spirit or 200 ml wine or 500 ml beer).

xv.   Subject with smoking history of > 10 Cigarettes / day or Tobacco consumption > 4 packets / day.

xvi.   Subject who has participated in any other clinical trial requiring repeated blood sampling or a blood donation program or blood loss of more than 450 ml, in the past three months (approx. 90 days) (This 450 ml includes the total blood loss that will occur during the study).

xvii.   Subject with clinically significant abnormal lab values.

xviii.   Female subjects of childbearing age or nursing women

xix.   Subjects working in radiation area or any individual who has received more than the permissible amount of radiation in the past 12 months.

|Pre-study Screening

Demographic Data, Medical and Medication history, General and Systemic Physical Examination, Hematology, Biochemistry, Serology and Urine Analysis.

|Admission and stay

After receiving signed informed consent document, each study subject will be assigned a unique ID to ensure their identity remains confidential. Subjects will be housed for at least 2 hours before drug administration until 12 hours after drug administration. If necessary, subjects will be called back the next day for Gamma Imaging at the 20-hour and 24-hour marks.

|Administration of Investigational products:

A single oral dose of the investigational product (Etoricoxib 60mg + Paracetamol 325mg Table) surface labeled with Technetium -99mTc will be administered to the subjects in a sitting posture with 240 ml of drinking water at ambient temperature during the study under supervision of trained study personnel. The clinical staff (dosing personnel) will ensure that the study participant has swallowed medication by performing mouth check using torchlight and spatula to assess compliance to dosing. Investigational products must be swallowed whole and must not be chewed, crushed or divided.

|Gamma Imaging Schedule

Sequential static imaging- shall be performed at 00.00 (Within 05 Minutes of dosing), 01:00, 02.00, 04.00, 06.00, 8.00, 10.00, and 12.00 hours post dose for two minutes. Gamma Imaging can be stopped, as soon as colon transit is achieved. Additional images can be taken as per investigator discretion without discomfort to subject. For post dose Gamma Imaging will be performed with a window period of ± 05 minutes.

|Food and fluid restrictions:

Water will be restricted from at least 01 hour prior to dosing until at least 01-hour post-dose (except for water given with dosing).

Subjects should not consume alcohol and smoke 48 hours before drug administration and throughout study period. Subject should not consume grapefruit containing products for 48 hours before the drug administration and throughout the study.

|Posture restrictions**:**

Subject will remain in semi recumbent position on bed for initial 06 hours post-dose and only necessary movement will be allowed during this period. Thereafter subjects will be allowed to ambulate freely during the remainder of the study.

|Collection of blood samples:

In this study, total 2 (10 X 2 ml each) blood samples will be collected for Screening Sample and Post study Safety Sample.

The pre-dose blood sample for screening shall be taken upto 120 minutes prior to dosing.

|Other Samples

Blood volume upto 10 ml and urine volume of upto 25 ml for additional or repeat clinical laboratory tests will be taken if necessary.

|Handling of blood samples:

After collection, the blood samples will be placed in an ice bath or other chilling device until centrifugation. Blood samples will be placed in a refrigerated centrifuge within 45 minutes of blood sample collection.

|Safety Assessment:

Vital signs:

·  Sitting blood pressure, pulse rate and body temperature will be measured at the time of check-in and prior to check-out. Subjects must have vital signs clinically acceptable prior to check-in to study.

·  Sitting blood pressure, pulse rate and body temperature will be measured prior to dosing and during the study.

·  Sitting /supine blood pressure, pulse rate and body temperature will be measured at 6.0 and 10.0 hours (± 30 minutes) post dose and as needed in study.

Subject having sitting systolic blood pressure less than 100 mmHg or sitting diastolic blood pressure less than 60 mmHg during pre-dose will not be dosed.

***Clinical examination:***At the time of check-in and prior to check-out in study and during the study.

Well Being assessment:

Subjects will be advised to report any AE and will be specifically asked by trained study personnel in a non-leading manner about any AE at the time of clinical examinations, during vital signs recording, at about 6.0 & 10.0 hours post dose and as needed and during study. Necessary treatment of an AE will be performed by the Investigator or physician and recorded.

All dosed study subjects will be assessed for clinical examination including vital sign (sitting blood pressure, pulse rate and body temperature) and laboratory tests at the end of the study or as applicable.

|Analytical methodology: Parameters studied by Scintigraphy

The following parameters will be evaluated using images captured by a Gamma camera (99mTc-based Scintigraphy):

·        Time required for the radiolabelled investigational product to disintegrate in the GIT

·        Location of disintegration in the GIT

·        Location of the radiolabelled investigational product in the GIT at the specified time intervals

·        Gastric residence time

·        Intestinal arrival time

|Statistical Analysis:

Statistical analysis will be performed on the observed parameters using suitable statistical software.

|Compensation

As approved by the IEC.

|Study Report

The report will be prepared after completion of the study as per norms.