CTRI/2021/02/031284 [Registered on: 15/02/2021] Trial Registered Prospectively
Last Modified On:
23/12/2021
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical trial to study the effect of Topiroxostat Tablets in Patients with high uric acid levels in the blood.
Scientific Title of Study
"A Phase III, Prospective, Randomized, Double Blind, Single Dummy, Comparative, Parallel Group, Multicentric Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Topiroxostat Tablets Versus Allopurinol Tablets in Patients with Hyperuricemia with or without gout".
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CRPL/CT/19/010
Protocol Number
Version No.: 00 and Dated May 20, 2019
Other
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr A Appalaraju
Designation
Assistant Professor
Affiliation
Government Medical College & Govt. General Hospital (Old RIMS GGH)
Address
Department of Surgery (Urology Unit),
Government Medical College & Govt. General Hospital (Old RIMS GGH),
Srikakulam.
Srikakulam ANDHRA PRADESH 532001 India
Phone
9246666531
Fax
Email
draappalaraju@gmail.com
Details of Contact Person Scientific Query
Name
Mr Vipen Seth
Designation
President - Drug Regulatory Affairs
Affiliation
Precise Biopharma P. Limited
Address
Malwa, Unit No. 108,
E. S. Patanwala Industrial Estate, L.B.S. Marg, Ghatkopar (W),
Mumbai-400086.
Mumbai (Suburban) MAHARASHTRA 400086 India
Phone
8860833301
Fax
Email
vipen@precisegroup.co.in
Details of Contact Person Public Query
Name
Mr Vipen Seth
Designation
President - Drug Regulatory Affairs
Affiliation
Precise Biopharma P. Limited
Address
Malwa, Unit No. 108,
E. S. Patanwala Industrial Estate, L.B.S. Marg, Ghatkopar (W),
Mumbai-400086.
MAHARASHTRA 400086 India
Phone
8860833301
Fax
Email
vipen@precisegroup.co.in
Source of Monetary or Material Support
Precise Biopharma P. Limited
Malwa, Unit No. 108,
E. S. Patanwala Industrial Estate, L.B.S. Marg,
Ghatkopar (W),
Mumbai-400086, Maharashtra.
Primary Sponsor
Name
Precise Biopharma P Limited
Address
Malwa, Unit No. 108,
E. S. Patanwala Industrial Estate,
L.B.S. Marg, Ghatkopar (W),
Mumbai-400086, Maharashtra.
(1) ICD-10 Condition: E798||Other disorders of purine and pyrimidine metabolism,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Allopurinol Tablets 100 mg
Patients will be advised to take one tablet twice daily orally, swallowed as a whole with water in the morning and evening around same time every day for 16 weeks.
Intervention
Topiroxostat Tablets 20 mg / 40 mg / 60 mg
Patients will be advised to take one tablet twice daily orally, swallowed as a whole with water in the morning and evening around same time every day for 16 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or female patients aged between 18 to 65 years (both inclusive).
2. Treatment naïve patients with diagnosis of Hyperuricemia (serum uric acid level >7 mg/dL) with or without gout and in the opinion of the Investigator, require treatment for hyperuricemia where uric acid deposition has already occurred (including a history or presence of tophus and/or gouty arthritis).
3. Patients with history of gout will be defined by ACR/EULAR 2015 criteria.
4. Patients with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
5. Patients willing to comply with the protocol requirements.
ExclusionCriteria
Details
1. Patients with suspected hypersensitivity to the study medication or any of the ingredients of the formulation.
2. Pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.
3. Females who are not ready to use acceptable contraceptive methods during the course of study.
4. Patients with the history and onset of gout flares /gouty arthritis within 2 week prior to start of the study drug administration.
5. Patients with hyperuricemia secondary to certain disorders (i.e., history of hematologic disorders, Lesch-Nyhan syndrome and Down’s syndrome).
6. Patient with history of xanthinuria.
7. Patient with history of secondary gout joint diseases induced by rheumatoid arthritis, psoriatic arthritis and bone tumor.
8. Patients who requires therapy with prednisone > 10 mg/ day during the study.
9. Clinically Significant abnormal physical, laboratory, ECG findings or history at the screening examination, which would interfere with the study objectives.
10. Patients with Type 1 Diabetes will be excluded from the study.
11. Patients with Type 2 Diabetes Mellitus whose diabetes has not been stable and controlled for the previous three months and with HbA1c value > 8% will be excluded from the study.
12. Patients with abnormal SGOT & SGPT with values more than 2.5X and Total Bilirubin 1.5X times the upper limit of normal.
13. Patients with abnormal eGFR (<60 mL/min/1.73 m2) will be excluded from the study [Estimated by Modification of Diet in Renal Disease (MDRD)].
14. Patients with severe hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg).
15. Patients with a history of angina, Myocardial Infarction (MI) or stroke within last 6 months prior to screening.
16. Patients with a history of New York Heart Association (NYHA) Class III or IV heart failure.
17. Patients with the history of hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure, or hospitalized transient ischemic attack will be excluded from the study.
18. Patients with the history of drug or alcohol abuse, presence of active peptic ulcer disease, thyroid disease, renal calculi or any significant medical condition that would interfere with the treatment and safety.
19. Patients with the history of hypersensitivity to NSAIDs.
20. Patients using other urate-lowering agents, Azathioprine, 6-Mercaptopurine, Theophylline, Vidarabin, Warfarin, Potassium, Chlorpromide, Cyclophosphamide, Phenytoin, Pentostatin, Captopril, Thiazides and Ampicillin and the study drug other than Topiroxostat.
21. Patients with history of any Oncological Conditions since last 5 years will be excluded from the study.
22. Patients with known case of infection with hepatitis B, hepatitis C or HIV.
23. Patients with concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
24. Subjects currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
25. Suspected inability or unwillingness to comply with the study procedures.
26. Any other condition that in the opinion of the Investigator that does not justify the patient’s participation in the study.
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Percent change in serum uric acid level from baseline to the final visit.
Day -3 (Visit 1) and Day 112 (Visit 6)
Secondary Outcome
Outcome
TimePoints
Proportion of patients with serum uric acid levels ≤ 6 mg/dL at the final visit.
Day 112 (Visit 6)
Percent change & change in serum uric acid level from baseline to the each visit.
Day -3 (Visit 1), Day 14 (Visit 3), Day 42 (Visit 4), Day 70 (Visit 5) and Day 112 (Visit 6)
Incidence of gout flares in each treatment group.
Day 14 (Visit 3), Day 42 (Visit 4), Day 70 (Visit 5) and Day 112 (Visit 6)
Adverse events & serious adverse events reported during the study.
Day 14 (Visit 3), Day 42 (Visit 4), Day 70 (Visit 5) and Day 112 (Visit 6)
Changes in the vital signs from baseline to end of the study visit.
Day -3 (Visit 1), Day 14 (Visit 3), Day 42 (Visit 4), Day 70 (Visit 5) and Day 112 (Visit 6)
Changes in clinical laboratory parameters from baseline to end of the study visit.
Day -3 (Visit 1) and Day 112 (Visit 6)
Target Sample Size
Total Sample Size="178" Sample Size from India="178" Final Enrollment numbers achieved (Total)= "188" Final Enrollment numbers achieved (India)="188"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
trial is a phase III, prospective, randomized, double blind, single dummy, comparative,
parallel group, multicentric clinical study to evaluate the efficacy, safety and
tolerability of Topiroxostat Tablets versus Allopurinol Tablets in patients with
hyperuricemia with or without gout.
Patients
who are willing and able to participate in the study will sign and date the
Informed Consent Form on the day of screening / baseline visit (Visit 1).
During this screening period, patients who are willing to give consent will be
evaluated for all the eligibility criteria. Eligible patients aged between 18
to 65 years (both inclusive), who are treatment naïve with diagnosis of hyperuricemia
(serum uric acid level >7 mg/dL) with or without gout will be considered for
the study.
After
confirming the inclusion/exclusion criteria the subject will be randomized and
provided with study medication at randomization visit. Patients will be
provided with patient diary at randomization visit, which need to be brought
along with in each subsequent visit till the last visit. Follow up visits will
be done on week 2/day 14(±2), week 6/day 42(±2), week 10/day 70(±2) and week
16/day 112(±2) (Final Visit) of treatment to assess efficacy, safety and
tolerability.
Patients
will be assigned to either of the two arms i.e. Arm A or Arm B consisting of
Topiroxostat Tablets or Allopurinol Tablets. Patients will be given the study
medication twice daily for 16 weeks.
Patients
will be advised to take one tablet twice daily orally, swallowed as a whole
with water in the morning and evening around same time every day for 16 weeks.
Patients
will be advised to maintain sufficient fluid intake during the study.
The
dose up-titration method used in this study to minimize the risk of gouty
arthritis arising in association with rapid serum uric acid reduction. The
dosage of Allopurinol in the study will be set as 100 mg/day for the first 2
weeks and then 200 mg/day for 14 weeks. The dosage of Topiroxostat in the study
will be set as 40 mg/day for the first 2 weeks and then 80 mg/day for 4 weeks,
and 120 mg/day for 10 weeks.
Topiroxostat
Tablets
20
mg - Twice Daily for first 2 weeks
40
mg - Twice Daily for next 4 weeks
60
mg - Twice Daily for next 10 weeks
Allopurinol
Tablets
100
mg - Once Daily + Placebo Tablet - Once Daily for first 2 weeks