Study to Assess the Effects of FX006 on Blood Glucose in Patients With OA of the Knee and Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT02762370
• Recruitment Status: Completed
• First Posted: May 4, 2016
• Results First Posted: January 26, 2018
• Last Update Posted: January 26, 2018
• Sponsor: Flexion Therapeutics, Inc.
• Information provided by (Responsible Party): Flexion Therapeutics, Inc.

Study Description

Brief Summary:

The purpose of this study was to compare the effects of FX006 and Triamcinolone Acetonide Injectable Suspension, United States Pharmacopeia (USP) (referred to as TCA IR in the protocol) on blood glucose (BG) in patients with osteoarthritis (OA) of the knee and Type 2 diabetes mellitus (DM).

Condition or disease	Intervention/treatment	Phase
Osteoarthritis of the Knee; Type 2 Diabetes Mellitus	Drug: FX006 32 mg; Drug: TCA IR 40 mg	Phase 2

Detailed Description:

This study employed a double-blind, randomized, parallel group, single dose design to explore the pharmacodynamic effects on BG levels in type 2 diabetics following IA administration of 32 mg FX006 compared to 40 mg TCA IR. The study was conducted in male and female patients ≥40 years of age with OA of the knee and type 2 DM not managed by injectable agents. In order to be eligible for study participation, patients were to be treated with 1 or 2 oral agents and have hemoglobin A1c (HbA1c) levels between 6.5%-9.0%.

Approximately 36 patients were planned to be randomized and treated to ensure there were at least 30 evaluable patients (15 patients on FX006 and 15 patients on TCA IR). Patients were randomized to 1 of 2 treatment groups (1:1) and treated with a single IA injection of either:

• 32 mg FX006 (18 patients) or
• 40 mg TCA IR (18 patients)

BG levels in each patient were evaluated for a total of 3 weeks (1 week prior to IA injection and 2 weeks post IA injection). After a screening visit, patients' BG levels were measured using a Dexcom Z4 Platinum Professional™ continuous glucose monitor (CGM) device, set to blinded mode, for up to 1 week pre-injection and for 2 weeks post injection using the same blinded CGM device. Patients also were provided with a Bayer Contour™ standard glucose measuring meter in order to perform the necessary calibrations per the manufacturer's recommendations. A final safety visit was planned at 6 weeks post-injection.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Parallel Group Comparison of the Effects of FX006 and TCA IR (Triamcinolone Acetonide Suspension) on Blood Glucose in Patients With Osteoarthritis of the Knee and Type 2 Diabetes Mellitus
• Study Start Date: April 2016
• Actual Primary Completion Date: October 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: FX006 32 mg; Single 5 mL intra-articular (IA) injection Extended-release Formulation	Drug: FX006 32 mg; Single 5 mL IA injection; Other Name: Zilretta
Active Comparator: TCA IR 40 mg; Single 1 mL intra-articular (IA) injection Immediate-release Formulation	Drug: TCA IR 40 mg; Single 1 mL IA injection; Other Names: Kenalog®-40 Injection; Triamcinolone Acetonide Crystalline Suspension (TAcs)

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline for Average Blood Glucose (mg/dL) [ Time Frame: Baseline and 72 Hours post intra-articular (IA) injection ]
   Average blood glucose was analyzed with a mixed model for repeated measures (MMRM)

Secondary Outcome Measures :

1. Percent Time Blood Glucose Less Than 70 mg/dl, 70 - 180 mg/dl, 180.1 - 250.0 mg/dl, 250.1 - 350.0 mg/dl, and Greater Than 350.0 mg/dl [ Time Frame: Baseline to Days 1-3 ]
   The glycemic variability was calculated as the coefficient of variation (CV) of the hourly averages in each of these time periods: Hour 1-24, Hour 1-48, Hour 1-72, Hour 1-168, and Hour 1-360. The % CV for each patient was derived using the formula: (SD/mean)*100, using the values for each hourly average glucose measurement over the time period. Average % CV in the FX006 40 mg group was compared to the TCA IR 40 mg group using a linear model (ANCOVA) with fixed effects for treatment group. Model covariates were study center and baseline (72-hour) blood glucose average.
2. Glycemic Variability Coeffecient of Variation (CV) [ Time Frame: Baseline to 72 hours post injection (hourly average blood glucose measurement over the time period) ]
   The glycemic variability was calculated as the coefficient of variation (CV) of the hourly averages in each of these time periods: Hour 1-24, Hour 1-48, Hour 1-72, Hour 1-168, and Hour 1-360. The % CV for each patient was derived using the formula: (SD/mean)*100, using the values for each hourly average glucose measurement over the time period. Average % CV in the FX006 40 mg group was compared to the TCA IR 40 mg group using a linear model (ANCOVA) with fixed effects for treatment group. Model covariates were study center and baseline (72-hour) blood glucose average.
3. Area Under the Effect (AUE) Curves for Average Blood Glucose - FX006 Versus TCA IR [ Time Frame: Baseline to 72 hours post injection (-72 hr, 0 hr, and 1, 2, 3, 7, and 15 days post-dose) ]

Other Outcome Measures:

1. Percent Time Blood Glucose Less Than 70 mg/dl, 70 - 180 mg/dl, 180.1 - 250.0 mg/dl, 250.1 - 350.0 mg/dl, and Greater Than 350.0 mg/dl [ Time Frame: Baseline to Days 1-2 ]
2. Change From Baseline for Maximum Blood Glucose: Baseline Average Blood Glucose (Hour -72 to Hour -1) to Maximum Blood Glucose (Hour 1 to Hour 72) for FX006 32 mg Relative to TCA IR 40 mg [ Time Frame: Baseline (Hour -72 to Hour -1) to Hour 1 to Hour 72 ]
3. Change in Average Blood Glucose From Baseline (Hour -48 to Hour -1) to Hour 1 to Hour 48 for FX006 32 mg Relative to TCA IR 40 mg. [ Time Frame: Baseline (Hour -48 to Hour -1) to Hour 1 to Hour 48 ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions
• Male or female ≥40 years of age
• Type 2 diabetes mellitus for at least 1 year prior to Screening and not managed with injectable agents (e.g. insulin or insulin analogs, exenatide, pramlintide, liraglutide)
• Currently treated with 1 or 2 oral agents for diabetes, with stable doses for at least 2 months
• HbA1c ≥6.5% and ≤ 9.0%
• Currently meets American College of Rheumatology (ACR) Criteria (clinical or radiological) for OA.
• Symptoms associated with OA of the knee for ≥ 6 months prior to Screening
• Index knee pain on most days (>15) over the last month (as reported by the patient)
• Body mass index (BMI) ≤ 40 kg/m2
• Willingness to abstain from use of protocol-specified restricted medications during the study
• Willingness to wear a CGM device uninterrupted for 24 hours per day throughout the study, remain with receiving range and comply with calibration requirements
• Accustomed to using a Standard Blood Glucose Measuring device by finger stick

Exclusion Criteria:

• Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or arthritis associated with inflammatory bowel disease
• History of infection in the index knee joint
• Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening
• Presence of surgical hardware or other foreign body in the index knee
• Unstable joint (such as a torn anterior cruciate ligament) within 12 months of screening
• IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening
• IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening
• IV or intramuscular (IM) corticosteroids (investigational or marketed) within 3 months of Screening
• Oral corticosteroids (investigational or marketed) within 1 month of Screening
• Inhaled, intranasal or topical corticosteroids (investigational or marketed) within 2 weeks of Screening
• Any other IA investigational drug/biologic within 6 months of Screening
• Prior use of FX006
• Use of acetaminophen, or acetaminophen containing products
• Current use of a continuous glucose monitoring device
• Women of child-bearing potential not using effective contraception or who are pregnant or nursing

Contacts and Locations

Locations

United States, California

Anaheim, California, United States, 92801

El Cajon, California, United States, 92020

North Hollywood, California, United States, 91606

United States, Pennsylvania

Duncansville, Pennsylvania, United States, 16635

United States, South Carolina

Mount Pleasant, South Carolina, United States, 29464

United States, Tennessee

Knoxville, Tennessee, United States, 37938

United States, Texas

Dallas, Texas, United States, 75231

San Antonio, Texas, United States, 78258

Sponsors and Collaborators

Flexion Therapeutics, Inc.

Investigators

• Study Director: Neil Bodick, MD; Flexion Therapeutics

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Russell SJ, Sala R, Conaghan PG, Habib G, Vo Q, Manning R, Kivitz A, Davis Y, Lufkin J, Johnson JR, Kelley S, Bodick N. Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Rheumatology (Oxford). 2018 Dec 1;57(12):2235-2241. doi: 10.1093/rheumatology/key265.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02762370
• Other Study ID Numbers: FX006-2015-010
• First Posted: May 4, 2016
• Results First Posted: January 26, 2018
• Last Update Posted: January 26, 2018
• Last Verified: December 2017

Keywords provided by Flexion Therapeutics, Inc.:

osteoarthritis; knee; pain; diabetes; intra-articular; injection; corticosteroid

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; FX006; Triamcinolone diacetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action