| CTRI Number |
CTRI/2008/091/000254 [Registered on: 28/11/2008] |
| Last Modified On: |
12/12/2012 |
| Post Graduate Thesis |
|
| Type of Trial |
Interventional |
Type of Study
Modification(s)
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
A clinical study to study the effects of the drug TZP-101 in patients with severe gastroparesis (delayed gastric emptying)due to Diabetes Mellitus |
Scientific Title of Study
Modification(s)
|
A Multicenter, Randomized, Double-Blind, Placebo-Controlled,Dose-Ranging Study to Assess the Efficacy and Safety of TZP-101 when Administered as a 30 Minute I.V. Infusion to Subjects with Severe Gastroparesis due to Diabetes Mellitus |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| NCT00612014 |
ClinicalTrials.gov |
| TZP-01-CL-G004 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Dr V Balakrishnan |
| Designation |
Principal Investigator |
| Affiliation |
Amrita Institute of Medical Sciences and Research Center |
| Address |
Amrita Institute of Medical Sciences and Research Center, Amrita Lane, Elamakkara PO
Ernakulam
KERALA
682026
India |
| Phone |
91-9847243560 |
| Fax |
91-484-2802020 |
| Email |
vbalakrishnan@aims.amrita.edu |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Naveena A DCor |
| Designation |
Medical Safety Officer |
| Affiliation |
QED Pharmaceutical Services, Pvt. Ltd., Hyderabad |
| Address |
QED Pharmaceutical Services, Pvt. Ltd., Plot No. 8-2-684/4/16, Road No.12, Anand Banjara Lane, Banjara Hills
Hyderabad
ANDHRA PRADESH
500034
India |
| Phone |
91-040-23304916 |
| Fax |
91-40-2330491 |
| Email |
naveena.dcor@qedpharma.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Capt A Venkat Rao Retd |
| Designation |
Director Operations |
| Affiliation |
QED Pharmaceutical Services Pvt. Ltd. |
| Address |
Director Operations, QED Pharmaceutical Services Pvt. Ltd., Plot No.8-2-684/4/16, Road No 12, Banjara Hills
Hyderabad
ANDHRA PRADESH
500034
India |
| Phone |
91-40-23302723 |
| Fax |
91-40-23304917 |
| Email |
rao.ancha@qedpharma.com |
|
Source of Monetary or Material Support
Modification(s)
|
| Tranzyme, Inc.
4819 Emperor Blvd.
Suite 400
Durham, NC 27703, USA |
|
Primary Sponsor
Modification(s)
|
| Name |
Tranzyme Inc |
| Address |
Tranzyme Inc.4819 Emperor Blvd.Suite 400Durham, NC 27703, USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
|
Countries of Recruitment
Modification(s)
|
India
Denmark
Norway
Sweden
United Kingdom
United States of America |
Sites of Study
Modification(s)
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DrV Balakrishnan |
Amrita Institute of Medical Sciences and Research Center |
Amrita Institute of Medical Sciences and Research Center, Amrita Lane, Elamakkara PO, Cochin, Kerala-682026
Ernakulam
KERALA |
04844001225
04842802020
vbalakrishnan@aims.amrita.edu |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, Amrita Institute of Medical Sciences & Research Centre, Cochin |
Approved |
|
Regulatory Clearance Status from DCGI
Modification(s)
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
Severe gastroparesis due to Diabetes Mellitus, |
|
Intervention / Comparator Agent
Modification(s)
|
| Type |
Name |
Details |
| Comparator Agent |
Placebo - 5% dextrose in water |
60 ml IV infusion over 30 minutes |
| Intervention |
TZP-101 |
40/80/160/320/600 micrograms/kg iv 2ml/minute for 30 minutes
1 infusion/day for 4 consecutive days
|
|
Inclusion Criteria
Modification(s)
|
| Age From |
18.00 Year(s) |
| Age To |
80.00 Year(s) |
| Gender |
Both |
| Details |
Subjects who meet all of the following inclusion criteria may be enrolled in the study:
1. Subject (male or female) is 18-80 years old
2. Subject has type 1 or type 2 diabetes mellitus
3. Subject has documented diagnosis of gastroparesis (all of the following apply):
a) Confirmed delayed gastric emptying (see Appendix IV; also, properly conducted gastric emptying assessment within prior 6 months acceptable)
b) AND a minimum 3 month history of relevant symptoms for
gastroparesis (chronic post-prandial fullness, bloating, epigastric discomfort, early satiety, belching after meal, post-prandial nausea, vomiting).
c) AND a Gastroparesis Cardinal Symptom Index (GCSI) total score of ≥ 2.66 and a post-prandial fullness/early satiety subscale score of ≥ 3.00
d) AND it is confirmed by endoscopy that there are no obstructive lesions in the esophagus or stomach (endoscopy within 3 prior months acceptable)
4. Subject has never had a gastrectomy, nor major abdominal surgery or any evidence of bowel obstruction within previous 12 months
5. Dosage of any concomitant medications has been stable for at least 3 weeks
6. HbA1c level is ≤ 12.5%
7. Subject has a BMI < 35
8. Subject body weight is ≤ 110 kg
9. Subject uses adequate contraception |
|
| ExclusionCriteria |
| Details |
Subjects who meet none of the following exclusion criteria may be enrolled in the study:
1. Subject has acute severe gastroenteritis
2. Subject has a gastric pacemaker
3. Subject is on chronic parenteral feeding
4. Subject has daily persistent severe vomiting
5. Subject has pronounced dehydration
6. Subject has had diabetic ketoacidosis in last 4 weeks
7. Subject has a history of eating disorders (anorexia nervosa, binge eating, bulimia)
8. Subject has a marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval >450 ms for male / >470 ms for female)
9. Subject has a history of additional risk factors for Torsades de Pointes (heart failure, chronic hypokalemia, family history of Long QT Syndrome)
10. Subject requires use of concomitant medication that prolongs the QT interval
11. Subject has history of cardiovascular ischemia in previous 12 months or acute myocardial infarction (MI) or unstable angina
12. Subject requires use of concomitant medication that is known to interact with isoenzyme CYP3A4 and the combination with an CYP3A4 inhibitor is known to introduce a clinically significant drug interaction
13. Subject has a history of psychiatric disorder or cognitive impairment that would interfere with participation in the study
14. Subject has a history of alcoholism
15. Subject is taking regular daily narcotics
16. Subject has a known history of Hep B, Hep C or HIV
17. Subject has severely impaired renal function (creatinine clearance < 30 mL/min)
18. Subject has severe impairment of liver function, defined as albumin level ≤ 2.5 gm/dL and/or prothrombin time >6 seconds over control (INR > 2.3)
19. Subject has participated in an investigational study within 30 days prior to or received TZP-101 within 90 days prior to study initiation
20. Subject is pregnant or is breast-feeding |
|
Method of Generating Random Sequence
Modification(s)
|
Adaptive randomization, such as minimization |
Method of Concealment
Modification(s)
|
On-site computer system |
Blinding/Masking
Modification(s)
|
Participant, Investigator and Outcome Assessor Blinded |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Change from baseline in the mean Gastroparesis Cardinal Symptom Index score (24 hour recall version) across the four days of dosing. Baseline is the average of the scores collected across the 4 days just prior to admission for dosing. |
Time Frame: after 4 dosing days
|
|
Secondary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| Cumulative Gastroparesis Symptoms Assessment (GSA) score after each dosing event and after all dosing events |
Time Frame: every 30 minutes for 4 hours |
| Change from baseline in mean GCSI total score |
Time Frame: after 4 dosing days |
| Change from baseline in the mean of any of the four GCSI post-prandial fullness/early satiety subscale score items (stomach fullness, not able to finish a normal-sized meal,feeling excessively full after meals, loss of appetite) across the four days of dosing |
Each of the 4 dosing days |
| Change from baseline gastric emptying rate |
Time Frame: After 4 dosing days |
|
Target Sample Size
Modification(s)
|
Total Sample Size="78"
Sample Size from India="0"
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
Modification(s)
|
Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
Date Missing |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
21/10/2005 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
Estimated Duration of Trial
Modification(s)
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
Publication Details
Modification(s)
|
None |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
Brief Summary
Modification(s)
|
This is a multicenter, randomized, double-Blind, placebo-Controlled, parallel group, dose-Ranging study to assess the efficacy and safety of TZP-101 in subjects with severe gastroparesis due to diabetes mellitus. TZP-101 will be administered as a 40/80/160/320/600 micrograms/kg, 30 Minute I.V. Infusion once daily for 4 days. Upto 100 patients (The sample size will be determined by adaptive randomization) will be enrolled in the study that will be conducted in approximately 15 centers in US and Europe and 3 centers in India. In India, upto 30 patients will be enrolled. Recruitment in India is expected to start by end of November 2008. Primary Outcome Measures: Change from baseline in the mean Gastroparesis Cardinal Symptom Index score (24 hour recall version) across the four days of dosing. Baseline is the average of the scores collected across the 4 days just prior to admission for dosing. [ Time Frame: after 4 dosing days ] Secondary Outcome Measures: Cumulative GSA score after each dosing event and after all dosing events [ Time Frame: every 30 minutes for 4 hours on each of the 4 dosing days] Change from baseline in mean GCSI total score (Time Frame: after 4 dosing days) Change from baseline in the mean of any of the four GCSI post-prandial fullness/early satiety subscale score items (stomach fullness, not able to finish a normal-sized meal,feeling excessively full after meals, loss of appetite) across the four days of dosing Change from baseline gastric emptying rate. (Time Frame: After 4 dosing days).study terminated |