A clinical trial to study the effect of Topiroxostat Tablets in Patients with high uric acid levels in the blood.

Phase 3

Completed

• Conditions: Other disorders of purine and pyrimidine metabolism,

• Registration Number: CTRI/2021/02/031284
• Lead Sponsor: Precise Biopharma P Limited

Brief Summary

Thistrial is a phase III, prospective, randomized, double blind, single dummy, comparative,parallel group, multicentric clinical study to evaluate the efficacy, safety andtolerability of Topiroxostat Tablets versus Allopurinol Tablets in patients withhyperuricemia with or without gout.

 Patientswho are willing and able to participate in the study will sign and date theInformed Consent Form on the day of screening / baseline visit (Visit 1).During this screening period, patients who are willing to give consent will beevaluated for all the eligibility criteria. Eligible patients aged between 18to 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 forthe study.

 Afterconfirming the inclusion/exclusion criteria the subject will be randomized andprovided with study medication at randomization visit. Patients will beprovided with patient diary at randomization visit, which need to be broughtalong with in each subsequent visit till the last visit. Follow up visits willbe done on week 2/day 14(±2), week 6/day 42(±2), week 10/day 70(±2) and week16/day 112(±2) (Final Visit) of treatment to assess efficacy, safety andtolerability.

 Patientswill be assigned to either of the two arms i.e. Arm A or Arm B consisting ofTopiroxostat Tablets or Allopurinol Tablets. Patients will be given the studymedication twice daily for 16 weeks.

 Patientswill be advised to take one tablet twice daily orally, swallowed as a wholewith water in the morning and evening around same time every day for 16 weeks.

 Patientswill be advised to maintain sufficient fluid intake during the study.

 Thedose up-titration method used in this study to minimize the risk of goutyarthritis arising in association with rapid serum uric acid reduction. Thedosage of Allopurinol in the study will be set as 100 mg/day for the first 2weeks and then 200 mg/day for 14 weeks. The dosage of Topiroxostat in the studywill 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.

 **TopiroxostatTablets**

20mg - Twice Daily for first 2 weeks

40mg - Twice Daily for next 4 weeks

60mg - Twice Daily for next 10 weeks

 **AllopurinolTablets**

100mg - Once Daily + Placebo Tablet - Once Daily for first 2 weeks

100mg - Twice Daily for next 14 weeks

Detailed Description

Not available

Study Timeline

• Study Completion: 2021-01-11
• Study Start: 2021-02-15
• Last Update Posted: 2021-12-23

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 178

Inclusion Criteria

• Male or female patients aged between 18 to 65 years (both inclusive).
• 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).
• Patients with history of gout will be defined by ACR/EULAR 2015 criteria.
• Patients with ability to understand and provide written informed consent form, which must have been obtained prior to screening.
• Patients willing to comply with the protocol requirements.

Exclusion Criteria

• Patients with suspected hypersensitivity to the study medication or any of the ingredients of the formulation.
• Pregnant or breast-feeding, or expecting to conceive within the projected duration of the study.
• Females who are not ready to use acceptable contraceptive methods during the course of study.
• Patients with the history and onset of gout flares /gouty arthritis within 2 week prior to start of the study drug administration.
• Patients with hyperuricemia secondary to certain disorders (i.e., history of hematologic disorders, Lesch-Nyhan syndrome and Down’s syndrome).
• Patient with history of xanthinuria.
• Patient with history of secondary gout joint diseases induced by rheumatoid arthritis, psoriatic arthritis and bone tumor.
• Patients who requires therapy with prednisone > 10 mg/ day during the study.
• Clinically Significant abnormal physical, laboratory, ECG findings or history at the screening examination, which would interfere with the study objectives.
• Patients with Type 1 Diabetes will be excluded from the study.
• 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.
• Patients with abnormal SGOT & SGPT with values more than 2.5X and Total Bilirubin 1.5X times the upper limit of normal.
• 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)].
• Patients with severe hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg).
• Patients with a history of angina, Myocardial Infarction (MI) or stroke within last 6 months prior to screening.
• Patients with a history of New York Heart Association (NYHA) Class III or IV heart failure.
• Patients with the history of hospitalized unstable angina, cardiac or cerebrovascular revascularization procedure, or hospitalized transient ischemic attack will be excluded from the study.
• 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.
• 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.
• Patients with history of any Oncological Conditions since last 5 years will be excluded from the study.
• Patients with known case of infection with hepatitis B, hepatitis C or HIV.
• Patients with concurrent participation in another clinical trial or any investigational therapy within 90 days prior to signing informed consent.
• Subjects currently taking any of the prohibited medications(s) and inability/unwillingness to discontinue them for the entire study period.
• Any other condition that in the opinion of the Investigator that does not justify the patient’s participation in the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percent change in serum uric acid level from baseline to the final visit.	Day -3 (Visit 1) and Day 112 (Visit 6)

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (16)

Anu Hospitals; 🇮🇳 Krishna, ANDHRA PRADESH, India

B.J. Medical College & Civil Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Gandhi Medical College & Hospital; 🇮🇳 Hyderabad, TELANGANA, India

Government Medical College & Govt. General Hospital (Old RIMSGGH); 🇮🇳 Srikakulam, ANDHRA PRADESH, India

Grant Government Medical College; 🇮🇳 Mumbai, MAHARASHTRA, India

GSVM Medical College; 🇮🇳 Nagar, UTTAR PRADESH, India

Indira Gandhi Institute of Medical Sciences (IGIMS); 🇮🇳 Patna, BIHAR, India

Janam Multi-speciality Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Jawahar Lal Nehru (J.L.N) Medical College; 🇮🇳 Ajmer, RAJASTHAN, India

King Georges Medical University; 🇮🇳 Lucknow, UTTAR PRADESH, India

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Anu Hospitals

🇮🇳Krishna, ANDHRA PRADESH, India

Dr M Sateesh

Principal investigator

9491873197

drctresearch@gmail.com