| CTRI Number |
CTRI/2021/09/036239 [Registered on: 03/09/2021] Trial Registered Prospectively |
| Last Modified On: |
01/07/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
Bioavailability study to evaluate the pharmacokinetics safety and tolerability of Granisetron Sublingual Solution 1% |
|
Scientific Title of Study
|
An Open Label, Balanced, Randomized, Single-Dose, Three-Treatment, Three-Sequence, Three-Period, bioavailability study of Granisetron Sublingual Solution 1% w/v of Troikaa Pharmaceuticals Ltd., India and two different reference products Reference-1 Graniset 1 mg film-coated tablets of Sun Pharma Laboratories Ltd., India and Reference-2 Granicip 3 mg/3 ml solution for injection of Cipla Ltd., India in healthy, adult, human subjects under fasting condition |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 20-VIN-0329, V01, 10 Feb 2021 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Darshan Kharadi |
| Designation |
Principal Investigator |
| Affiliation |
Veeda Clinical Research Pvt. Ltd |
| Address |
Veeda Clinical Research Pvt. Ltd Shivalik Plaza Near I.I.M. Ambawadi Ahmedabad – 380015 Gujarat India Ahmadabad
GUJARAT 380015
India
Ahmadabad
GUJARAT
380015
India |
| Phone |
079-67773000 |
| Fax |
079-30013010 |
| Email |
darshan.kharadi@veedacr.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Arun Maseeh |
| Designation |
Sr. Vice President-Medical Services |
| Affiliation |
Troikaa Pharmaceuticals Ltd. |
| Address |
Troikaa Pharmaceuticals Ltd. Commerce House-I Satya Marg Bodakdev Ahmedabad -380054 Gujarat India
Ahmadabad GUJARAT 380054
India
Ahmadabad
GUJARAT
380054
India |
| Phone |
7926856242 |
| Fax |
|
| Email |
arunmaseeh@troikaapharma.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Arun Maseeh |
| Designation |
Sr. Vice President-Medical Services |
| Affiliation |
Troikaa Pharmaceuticals Ltd. |
| Address |
Troikaa Pharmaceuticals Ltd. Commerce House-I Satya Marg Bodakdev Ahmedabad -380054 Gujarat India
Ahmadabad GUJARAT 380054
India
GUJARAT
380054
India |
| Phone |
7926856242 |
| Fax |
|
| Email |
arunmaseeh@troikaapharma.com |
|
|
Source of Monetary or Material Support
|
| Troikaa Pharmaceuticals Ltd. Commerce House-I Satya Marg Bodakdev Ahmedabad-380054 Gujarat India |
|
|
Primary Sponsor
|
| Name |
Troikaa Pharmaceuticals Ltd |
| Address |
Commerce House-I Satya Marg Bodakdev Ahmedabad-380054 Gujarat India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Darshan Kharadi |
Veeda Clinical Research Pvt. Ltd |
Shivalik Plaza Near
I.I.M. Ambawadi Ahmedabad – 380015 Gujarat India Ahmadabad GUJARAT
Ahmadabad
GUJARAT |
07967773000
07930013010
darshan.kharadi@veedacr.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Anveshhan Independent Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
Nausea and Vomiting |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Granicip 3 mg/3 ml solution |
Granicip 3 mg/3 ml solution for injection of Cipla Ltd
10 mL of Granisetron 1 mg per 5 ml Injection is to be administered as a slow
intravenous bolus over not less than 30 seconds |
| Comparator Agent |
Graniset 1 mg tablets |
Graniset 1 mg tablets of Sun Pharma Laboratories Ltd. India
Two tablets of 1 mg each will be administered orally as a single dose with 240 mL of water |
| Intervention |
Granisetron Sublingual Solution 1% w/v |
Granisetron Sublingual Solution 1% w/v of Troikaa Pharmaceuticals Ltd., India
The pump must be primed prior to the first use. Each spray of Granisetron
Sublingual Solution delivers 0.1 ml of solution containing 1 mg Granisetron
after an initial priming of five sprays.
Two sprays of the dose should be administered under the tongue by pressing the button firmly and the mouth should be closed immediately after the dosing |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Both |
| Details |
1.Subjects aged between 18 and 45 years (both inclusive)
2.Subjects weight within normal range according to normal values for Body Mass Index (between 18.50 and 30.00 kg/m2) (both inclusive) with minimum of 50 kg weight.
3.Subjects with Haemoglobin ≥ 11.5 gm % at the time of screening
4.Subjects with normal health as determined by personal medical history, clinical examination and laboratory examinations within the clinically acceptable normal range.
5.Subjects having clinically acceptable 12-lead electrocardiogram (ECG).
6.Subjects having clinically acceptable chest X-Ray (PA view).
7.Subjects having negative urine screen for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine, and morphine).
8.Subjects having negative Urine alcohol /alcohol breath test.
9.Subjects willing to adhere to the protocol requirements and to provide written informed consent.
10.For male Subjects
Subjects willing to follow approved birth control methods (a double barrier method) for the duration of the study as judged by the investigator(s), such as (a double barrier method) condom with spermicide, Condom with diaphragm, or abstinence. Subjects should also not donate sperm during study period
11.Subjects having negative urine pregnancy test at screening and negative serum Beta-hCG Pregnancy test on admission day of period 01 (only for female subjects).
12.For Female Subjects
Female of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as intrauterine device (IUD), abstinence or double barrier contraception, i.e., condom + diaphragm, condom + spermicidal or foam
Postmenopausal for at least 1 year, or if less than 1 year, then following acceptable contraceptive measures as mentioned above
Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject). |
|
| ExclusionCriteria |
| Details |
1.Hypersensitivity to Granisetron or related class of drugs or any of its excipients or heparin.
2.History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, urogenital or psychiatric disease or disorder.
3.Any treatment which could bring about induction or inhibition of hepatic microsomal enzyme system within 1 month prior to dosing in period 01.
4.Presence of significant alcoholism or drug abuse.
5.History or presence of significant smoking (more than 10 cigarettes or beedis/day).
6.History or presence of asthma, urticaria or other significant allergic reactions.
7. History or presence of significant gastric and/or duodenal ulceration.
8.History or presence of significant thyroid disease, adrenal dysfunction, organic intracranial lesion such as pituitary tumor.
9.History or presence of cancer or basal or squamous cell carcinoma.
10.Difficulty with donating blood.
11. Difficulty in swallowing solids like tablets or capsules.
12.Use of any prescribed medication or OTC medication during last 30 days prior to dosing in period 01.
13.Major illness within past 3 months.
14.Volunteer who have donated blood (1 unit) or participation in a drug research study within past 90 days prior to the first dose of the study drug.
15.Consumption of xanthine-containing products, tobacco containing products or alcohol or alcoholic products for within 48 hours prior to dosing in period 01.
16.Consumption of grapefruit or grapefruit juice containing products within 72 hours prior to dosing of period 01.
17.Positive screening test for any one or more: HIV, Hepatitis B and Hepatitis C.
18.History or presence of significant easy bruising or bleeding.
19.History or presence of significant recent trauma.
20.Subjects who have been on an abnormal diet (for whatever reason) during the four weeks preceding the study.
21. Female subjects who are currently pregnant or breast feeding. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Other |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
The Plasma concentrations of Granisetron will be measured using validated LC-MS/MS bioanalytical method
Primary variables
Cmax AUC0-t
AUC0-inf |
Primary variables
Cmax, AUC0-t, AUC0-inf
2 min, 5 min, 10 min, 20 min, 30 min, 45 min and 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 7.00, 9.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hr |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Tmax AUC_%Extrap_obs t1/2
Kel |
2 min, 5 min, 10 min, 20 min, 30 min, 45 min and 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 5.00, 7.00, 9.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hr |
|
|
Target Sample Size
|
Total Sample Size="18"
Sample Size from India="18"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="0" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
04/10/2021 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
In recent
years, various methods have been developed to deliver therapeutic agents
through various transmucosal routes, to release a therapeutic amount of drug to
a specific site and to maintain the desired therapeutic concentration. The
conventional dosage forms, such as tablets or injections have many drawbacks
such as poor bioavailability, poor solubility, quick breakdown of the drug in
vivo, and rapid loss of drug activity. These drawbacks can be overcome through
a suitable delivery system, depending on the medical condition. The concept of
fast-dissolving films has become popular as a new delivery system. Several
approaches have been developed and implemented, to improve the therapeutic
outcomes of Granisetron HCl. A transdermal patch and extended release SC
injection has been prepared to control the release and provide better
therapeutic outcomes for the prevention of chemotherapy- induced N/V.
Similarly, Troikaa Pharmaceuticals Ltd. has formulate granisetron sublingual
solution to improve the therapeutic efficacy and bioavailability by avoiding
the first pass metabolism. We hereby propose to conduct bioavailability study
to evaluate the pharmacokinetic behavior of Granisetron sublingual solution 1%
w/v |