Efficacy and Safety of ATB-346 Versus Placebo in Osteoarthritis Patients

NCT03978208 | Completed Phase 2 DMC

• 1 other identifier: ATB-346-P2B-DRF
• Study Type: interventional
• Target: 381
• Locations: 1 country
• Sites: 35

Brief Summary

The primary objective of this study is to evaluate the efficacy of a 14-day dosing regimen of ATB-346 at doses of 150 mg, 200 mg and 250 mg compared to placebo in reducing osteoarthritis knee pain as measured by changes in the post-treatment WOMAC subscale pain score relative to each patient's pretreatment baseline WOMAC assessment.Safety will be assessed via measurements of vital signs and clinical laboratory tests at baseline and at various time points during the study, patient monitoring, and by the documentation of adverse events.

Conditions

Osteoarthritis

Keywords

Knee; WOMAC; NSAID; Pain

Outcome Measures

Primary Outcomes (1)

• 5-item pain intensity measure

  Self reported pain intensity over the past 48 hours. Each item is scored 0-10 (0 = no pain; 10 = pain as bad as can be), yielding a total between 0 and 50

  Previous 48 hours

Secondary Outcomes (5)

• 2-item stiffness intensity measure

  Previous 48 hours

• 17-item difficulty performing daily activities measure

  Previous 48 hours

• Measurement of whole blood cyclo-oxygenase activity

  After 1, 4 and 14 days of treatment dosing.

• Number of patients with genetic variations in the drug modifying enzyme CYP2C9 that may alter the metabolism of ATB-346 will be investigated.

  Samples will be retained through study completion and analyzed within 1 year of study initiation.

• Number of participants with treatment-related adverse events

  Pre-study and days 4, 14 and 24.

Study Arms (4)

Placebo Comparator

ACTIVE COMPARATOR

ATB-346 150 mg overencapsulated tablet taken by mouth once daily for 14 days

Drug: ATB-346 low dose

ATB-346 mid-dose

ACTIVE COMPARATOR

ATB-346 200 mg overencapsulated tablet taken by mouth once daily for 14 days

Drug: ATB-346 mid-dose

ATB-346 standard dose

ACTIVE COMPARATOR

ATB-346 250 mg overencapsulated tablet taken by mouth once daily for 14 days

Drug: ATB-346 standard dose

Active Comparator

PLACEBO COMPARATOR

Overencapsulated placebo tablet taken by mouth once daily for 14 days

Other: Placebo

Interventions

ATB-346 low dose DRUG

Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Also known as: Active comparator

Placebo Comparator

Placebo OTHER

Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Also known as: Non-active comparator

Active Comparator

ATB-346 mid-dose DRUG

Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Also known as: Active comparator

ATB-346 mid-dose

ATB-346 standard dose DRUG

Double blind comparison of orally administered ATB-346 versus placebo in osteoarthritis patients

Also known as: Active comparator

ATB-346 standard dose

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis greater than 2 years duration requiring the use of regular therapies, e.g. oral or topical anti-inflammatories, acetaminophen, topical capsaicin
• Between the ages of 40 to 75
• BMI ≤40
• Patients must be unlikely to procreate or agree to the use of acceptable contraceptive regimens from first drug administration , during the study, and for at least 30 days after the last dose
• Patients must not have used aspirin or naproxen-containing medications for 7 days prior to study entry
• Patients must not have used any anti-inflammatory medications or acetaminophen for 5 days prior to study entry
• Patients must show a ≥10-point increase in WOMAC Visual Analog Score between their screening visit and baseline study entry visit

You may not qualify if:

• Females who are pregnant or breastfeeding
• Seated and resting pulse rate less than 50 beats per minute (bpm) or more than 100 bpm at screening
• Seated and resting blood pressure below 100/60 mmHg or higher than 140/90 mmHg at screening
• History of significant hypersensitivity to naproxen, other non-steroidal anti-inflammatory agents, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Patients with a history of GI bleeding or ulceration
• Patients refractory to NSAIDs
• Presence of significant gastrointestinal, liver, or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or know to potentiate or predispose patients to undesired effects
• Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease as determined by the investigator
• Suicidal tendency, history of/or disposition to seizures, state of confusion
• History of hepatic disease
• Maintenance therapy with any drug, including gastroprotective agents such as proton pump inhibitors, H2 receptor antagonists, sucralfate, etc., or significant history of drug dependency or alcohol abuse (\>3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
• Any clinically significant illness in the previous 30 days before Day 1 of this study
• Use of any enzyme-modifying drugs, including strong inhibitors of CYP enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort) in the previous 30 days before Day 1 of this study
• Any history of tuberculosis and/or prophylaxis for tuberculosis
• Positive H. Pylori Urea Breathe Test

Sponsors & Collaborators

• Antibe Therapeutics Inc.: lead
• Veristat, Inc.: collaborator

Study Sites (35)

Viable Clinical Research Corp

Mission, British Columbia, V2V 1C6, Canada

Location

Ocean West Research Clinic

Surrey, British Columbia, V3Z 2N6, Canada

Location

James K. Lai MD Inc

Vancouver, British Columbia, V5Z 1K3, Canada

Location

Dr. MB Jones Inc

Victoria, British Columbia, V8V 4A1, Canada

Location

True North Clinical Research Inc.

Halifax, Nova Scotia, B3S 1M7, Canada

Location

Aggarwal and Associates Limited

Brampton, Ontario, L6T 0G1, Canada

Location

Manna Research (Burlington North)

Burlington, Ontario, L7M 4Y1, Canada

Location

Etobicoke Medical Centre

Etobicoke, Ontario, M8Z 5W4, Canada

Location

Dawson Clinical Research

Guelph, Ontario, N1H 1B1, Canada

Location

Dr. Allen Greenspoon Medicine Professional Corporation

Hamilton, Ontario, L8L 5G8, Canada

Location

Hamilton Medical Research Group

Hamilton, Ontario, L8M 1K7, Canada

Location

Milestone Research Inc.

London, Ontario, N5W 6A2, Canada

Location

KGK Science Inc

London, Ontario, N6A 5R8, Canada

Location

Malton Medical Clinic

Mississauga, Ontario, L4V 1P1, Canada

Location

SKDS Research Inc

Newmarket, Ontario, L3Y 5G8, Canada

Location

King Street Medical Clinic

Oshawa, Ontario, L1H 1G6, Canada

Location

Bluewater Clinical Research Group Inc

Sarnia, Ontario, N7T 4X3, Canada

Location

Viable Clinical Research Corp

Scarborough Village, Ontario, M1P 2T7, Canada

Location

Dr. Steven V. Zizzo Medicine Professional Corporation

Stoney Creek, Ontario, L8J 0B6, Canada

Location

Manna Research (Stoney Creek)

Stoney Creek, Ontario, L8J 3W2, Canada

Location

Canadian Phase Onward Inc.

Toronto, Ontario, M3J 0K2, Canada

Location

LMC Clinical Research Inc

Toronto, Ontario, M4G 3E8, Canada

Location

Manna Research (Toronto)

Toronto, Ontario, M9W 4L6, Canada

Location

Dr. Sabeen Anwar Medicine Professional Corporation

Windsor, Ontario, N8X 1T3, Canada

Location

Clinical Research& Arthritis Centre

Windsor, Ontario, N8X 2C9, Canada

Location

Devonshire Clinical Research Inc.

Woodstock, Ontario, N4S 5P5, Canada

Location

Manna Research (Quebec)

Lévis, Quebec, G6W 0M5, Canada

Location

Manna Research (Mirabel QC)

Mirabel, Quebec, J7J 2K8, Canada

Location

Recherche GCP Research

Montreal, Quebec, H1M 1B1, Canada

Location

Centre Medical Acadie

Montreal, Quebec, H4N 2W2, Canada

Location

Manna Research (Montreal)

Pointe-Claire, Quebec, H9R 4S3, Canada

Location

Diex Recherche Quebec Inc.

Québec, Quebec, G1N 4V3, Canada

Location

Centre de Recherche Saint-Louis

Québec, Quebec, G1W 4R4, Canada

Location

Diex Recherche Sherbrooke Inc.

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Diex Recherche Victoriaville Inc.

Victoriaville, Quebec, G6P 6P6, Canada

Location

MeSH Terms

Conditions

Osteoarthritis; Pain

Interventions

2-(6-methoxy-napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Deepen Patel, MD

  Veristat

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Overencapsulation of study drug tablets
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2019
• First Posted: June 7, 2019
• Study Start: March 29, 2019
• Primary Completion: December 29, 2019
• Study Completion: December 29, 2019
• Last Updated: July 21, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (35)