| CTRI Number |
CTRI/2020/04/024708 [Registered on: 17/04/2020] Trial Registered Prospectively |
| Last Modified On: |
07/04/2020 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
Phase-I bridging study of TRC041266 Powder in healthy human subjects. |
|
Scientific Title of Study
|
An Open Label, Randomized, Multiple-dose, Crossover Study to Compare the Oral
Pharmacokinetics and Safety of TRC041266 Powder with TRC4186 Tablet in Healthy
Human Subjects. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| PK-19-013, Version No. 1.0, Dated 10.12.2019 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Pradip Solanki |
| Designation |
Principal Investigator |
| Affiliation |
Bio-Evaluation Centre. |
| Address |
Bio-Evaluation Centre,
Torrent Pharmaceuticals Ltd.,
Village Bhat,
District-Gandhinagar
Gujarat, India
Gandhinagar
GUJARAT
382428
India |
| Phone |
07971315280 |
| Fax |
|
| Email |
pradipsolanki@torrentpharma.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Pradip Solanki |
| Designation |
Principal Investigator |
| Affiliation |
Bio-Evaluation Centre. |
| Address |
Bio-Evaluation Centre,
Torrent Pharmaceuticals Ltd.,
Village Bhat,
District-Gandhinagar
Gujarat, India
Gandhinagar
GUJARAT
382428
India |
| Phone |
07971315280 |
| Fax |
|
| Email |
pradipsolanki@torrentpharma.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Pradip Solanki |
| Designation |
Principal Investigator |
| Affiliation |
Bio-Evaluation Centre. |
| Address |
Bio-Evaluation Centre,
Torrent Pharmaceuticals Ltd.,
Village Bhat,
District-Gandhinagar
Gujarat, India
Gandhinagar
GUJARAT
382428
India |
| Phone |
07971315280 |
| Fax |
07923969135 |
| Email |
pradipsolanki@torrentpharma.com |
|
|
Source of Monetary or Material Support
|
| Torrent Pharmaceuticals Limited,Research Center, Village Bhat, Gandhinagar,Gujarat India 382428 |
|
|
Primary Sponsor
|
| Name |
Dr Sanjay Sharma |
| Address |
Torrent Pharmaceuticals Ltd.,
(Research Centre)
Village Bhat,
District Gandhinagar-382 428
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 Pradip Solanki |
Bio-Evaluation Centre, |
BE Centre Division,Torrent Pharmaceuticals Ltd.,Research centre,
Village Bhat,
District-Gandhinagar-382 428,
Gujarat, India
Gandhinagar
GUJARAT |
07971315280
07923969135
pradipsolanki@torrentpharma.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| ETHICS COMMITTEE SANJEEVANI HEART & MEDICAL HOSPITAL |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Healthy Human Volunteers |
Healthy Human Volunteers |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
TRC041266 Sachets |
TRC041266 Sachet (1500 mg) through oral route.
Eligible subjects will receive TRC041266 at a dose of 1500
mg or twice daily for 6
days (Day 1-6) followed by a single dose in the morning on day 7. |
| Comparator Agent |
TRC4186 Tablet |
TRC4186 Tablet (825 mg)through oral route.
Eligible subjects will receive TRC4186 (825 mg), twice daily for 6 days (Day 1-6) followed by a single dose in the morning on day 7. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Male and/or female subjects aged 18-65 years (both inclusive)
2. Volunteer with BMI of 18.5-30 kg/m2 (inclusive both) with minimum weight of 50 kg
3. Volunteer willing to provide written informed consent.
4. Ability to adhere to the study restrictions and assessments schedule |
|
| ExclusionCriteria |
| Details |
1. Inability to communicate or co-operate
2. History of angina, myocardial infarction (MI) or stroke within last 3 months prior to screening
3. Volunteers suffering from any chronic illness such as arthritis, asthma etc.
4. History of pre-existing bleeding disorder
5. Clinically relevant abnormal physical findings at the screening examination,
which would interfere with the objectives of the study
6. Clinically significant abnormalities in the results of the clinical laboratory tests (at screening or check-in day (i.e. Day-0))
7. Clinically significant abnormal ECG (at screening), 2D Echo or Chest X-ray
8. Pregnant or lactating women or female subjects who are of childbearing
potential and who are neither surgically sterilized nor willing to use reliable
contraceptive methods {i) bilateral tubal occlusion; ii) vasectomised partner and iii) sexual abstinence iv) barrier method of contraception} and/or female volunteer with positive urine pregnancy test
9. Smokers who are unable to stop tobacco consumption during each study period, or smokers who smokes >10 cigarettes (or equivalent) per Day during last 3 months prior to Day 1
10. Positive for HIV, HCV and HbsAg.
11. History of significant blood loss due to any reason, including blood donation in the past 3 months; or the total blood loss in the last 3 months, including for this study, exceeds 450 ml.
12. Participation in any study within past 3 months
13. Addiction to alcohol or history of alcohol or drug abuse
14. Intake of hepatic microsomal enzyme inducer/inhibitor drugs in the period
within 3 months prior to the first dose of study drug
15. History of consumption of prescribed medication since last 14 days or OTC medication/ herbal remedies since last 7 days before beginning of the study.
16. Volunteer found to be positive for breath alcohol test.
17. History of malignancy
18. Volunteer found to be positive for opiate, tetrahydrocannabinoid, amphetamine, barbiturates, benzodiazepines, cocaine based on urine test.
19. Systolic blood pressure less than 100 mmHg or more than 139 mmHg and diastolic blood pressure less than 60 mmHg or more than 89 mmHg.
20. Pulse rate less than 60/minute or more than 100/minute.
21. Oral temperature less than 95°F or more than 98.9°F.
22. Respiratory rate less than 10/minute or more than 20/minute.
23. History of hypersensitivity reaction/allergy to the investigational product or any drug chemically similar to the drug under investigation or any of the
excipients.
24. Recent history of kidney or liver dysfunction.
25. Volunteers suffering from any psychiatric (acute or chronic) disorder.
26. Existence of any surgical or medical condition, which, in the judgment of the chief investigator and/or clinical investigator /physician, might interfere with the absorption, distribution, metabolism or excretion of the drug or likely to compromise the safety of volunteers
27. Volunteers with left ventricular ejection fraction (LVEF) < 55%
28. Serum magnesium level more than 2.6 mg/dl in male and 2.5 mg/dl in female. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Pharmacy-controlled Randomization |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
To compare the oral pharmacokinetics of TRC041266
powder with TRC4186 tablet |
Day 1: 0.00 (pre-dose),0.25, 0.50, 1.00, 1.50, 2.00,2.50,
3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00 (pre-dose) (15 samples)
Day 2-6: 0.00 pre-dose (morning) and 12.00 pre-dose
(evening) (10 samples)
Day 7: 0.00 (pre-dose),0.25, 0.50, 1.00, 1.50, 2.00, 2.50,3.00, 3.50, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 24.00 hr(Day 8), 48 hr (Day 9) (17 samples). |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
a) To evaluate the safety and tolerability of TRC041266 powder in healthy human subjects.
b) To evaluate the pharmacokinetic parameters of metabolite M4 |
TRC041266 and metabolite M4 concentration data for study Day-1 and Day-7 (from 12 hrs
after morning dose).
Additional pharmacokinetic parameters based on full sampling (0-48 hrs) |
|
|
Target Sample Size
|
Total Sample Size="34"
Sample Size from India="34"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
01/07/2020 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
The study report shall form the basis of a manuscript for publication in a peerreviewed journal.
Credit will be given to all investigators in the study program with the written
consent of the sponsor. |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Despite considerable progress in the treatment of hyperglycaemia and hypertension, clinical trials reported the prevalence of Heart Failure in approximately 13-47% in diabetic patients . Even mild diastolic dysfunction has been found to be associated with eight times more risk of mortality compared with normal cardiac function i.e. after 1 year the mortality rate was around 20-30 while after 5 years the mortality increases up to 45-60%. One of the major causes of these complications is the formation of Advanced Glycosylation End (AGE) products. AGE is formed by a complex chain of reactions between reducing sugar such as glucose with proteins, forming multimeric complexes that trigger several pathological events. There are three main mechanisms responsible for the AGE-related complications : - non-receptor-mediated mechanisms including enhanced synthesis of extracellular matrix proteins, cross linking of structural proteins etc.
- receptor-mediated mechanisms such as promoting inflammation, endothelial dysfunction etc. and
- an increase in oxidative stress.
These underlying pathways lead to the complications of diabetes. An impaired vasodilatory reserve at the microvascular bed coupled to autonomic dysfunction contributing to a non-nutritive distribution of flow on one hand and a compromised myocardial diastolic reserve and contractile capacity along with impaired perfusion on the other, trigger a homeostatic imbalance and ultimately contribute to the accelerated progression of heart failure associated with diabetes. It is becoming increasingly clear that anti-AGE strategies have an important role to play in the treatment of people with diabetes. Torrent Pharmaceuticals Limited has developed a novel compound to address the main underlying mechanisms related to AGE-mediated complications. By reducing the preformed AGE and preventing AGE accumulation, the drug candidate TRC4186 would provide clinical benefit in heart failure secondary to diabetes by correcting the endothelial dysfunction, leading to an improved microvascular flow, and also by preserving function of myocardial calcium handling and preventing the deterioration in myocardial systolic and diastolic function. TRC4186 bioavailability is significantly reduced in the presence of food necessitating administration under fasting condition. Therefore, the parent molecule has been conjugated with decanoic acid as TRC041266 to form co-crystal to circumvent this problem Multiple dose comparative bioavailability study with TRC041266 powder and TRC4186 tablet in healthy volunteer is planned to evaluate pharmacokinetics and assess safety. |