Study to Assess the Effects of FX006 on Blood Glucose in... | NCT02762370

NCT02762370

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
FX006 32 mg	Experimental	Single 5 mL intra-articular (IA) injection Extended-release Formulation	Drug: FX006 32 mg
TCA IR 40 mg	Active Comparator	Single 1 mL intra-articular (IA) injection Immediate-release Formulation	Drug: TCA IR 40 mg

Name	Type	Description	Arm Group Labels	Other Names
FX006 32 mg	Drug	Single 5 mL IA injection	FX006 32 mg	Zilretta

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

Measure	Description	Time Frame
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	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.

Other Outcomes

Measure	Description	Time Frame
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		Baseline to Days 1-2
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

Eligibility Module

Eligibility 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/Locations Module

Name	Affiliation	Role
Neil Bodick, MD	Flexion Therapeutics	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Anaheim	California	92801	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30203101	Derived	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.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	FX006 32 mg	18 subjects received FX006 32 mg as a single 5 mL intra-articular (IA) injection
FG001	TCA IR 40 mg	15 subjects received triamcinolone acetonide injectable suspension, immediate release (TCA IR) 40 mg as a single 1 mL IA injection

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

ID	Title	Description
BG000	FX006 32 mg	FX006: Single 5 mL IA injection
BG001	TCA IR 40 mg	TCA IR: Single 1 mL IA injection
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00018 BG00115 BG00233

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00014.66± 7.032 OG00133.88± 6.612

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.0452														Superiority

Secondary

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

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.

Posted

Number

Percentage of time

Baseline to Days 1-3

ID	Title	Description
OG000	FX006 32 mg	Single 5 mL IA injection
OG001	TCA IR 40 mg	Single 1 mL IA injection

Units	Counts
Participants	OG000

Secondary

Glycemic Variability Coeffecient of Variation (CV)

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline to 72 hours post injection (hourly average blood glucose measurement over the time period)

ID	Title	Description
OG000	FX006 32 mg	Single 5 mL IA injection
OG001	TCA IR 40 mg	Single 1 mL IA injection

Units	Counts
Participants	OG000

Secondary

Area Under the Effect (AUE) Curves for Average Blood Glucose - FX006 Versus TCA IR

Posted

Least Squares Mean

Standard Error

hr*mg/dL

Baseline to 72 hours post injection (-72 hr, 0 hr, and 1, 2, 3, 7, and 15 days post-dose)

ID	Title	Description
OG000	FX006 32 mg	Single 5 mL IA injection
OG001	TCA IR 40 mg	Single 1 mL IA injection

Units	Counts
Participants	OG00018

Other Pre-specified

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

Posted

Number

Percentage of time

Baseline to Days 1-2

ID	Title	Description
OG000	FX006 32 mg	Single 5 mL IA injection
OG001	TCA IR 40 mg	Single 1 mL IA injection

Units	Counts
Participants	OG00018

Other Pre-specified

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

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline (Hour -72 to Hour -1) to Hour 1 to Hour 72

ID	Title	Description
OG000	FX006 32 mg	Single 5 mL IA injection
OG001	TCA IR 40 mg	Single 1 mL IA injection

Units	Counts
Participants	OG000

Other Pre-specified

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.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline (Hour -48 to Hour -1) to Hour 1 to Hour 48

ID	Title	Description
OG000	FX006 32 mg	Single 5 mL IA injection
OG001	TCA IR 40 mg	Single 1 mL IA injection

Units	Counts
Participants	OG00018

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FX006 32 mg	Drug: FX006 Single intra-articular injection FX006 32 mg	0	18	0	18	2	18
EG001	TCA IR 40 mg	Drug: TCA IR Single intra-articular injection TCA IR 40 mg	0	15	0	15	2	15

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected15 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected15 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected15 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0000 events0 affected18 at risk EG0011 events1 affected15 at risk
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0001 events1 affected18 at risk EG0010 events0 affected15 at risk

Subsequent to completion of clinical studies extensive testing was performed to assess the actual FX006 dose delivered. It was determined that the FX006 delivered dose to the patient from an FX006 40 mg vial is 32 mg.

Certain Agreements

ID	Term
D020370	Osteoarthritis, Knee
D003924	Diabetes Mellitus, Type 2
D010003	Osteoarthritis
D010146	Pain
D003920	Diabetes Mellitus

Ancestor Terms

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000631825	FX006
D014221	Triamcinolone

ID	Term
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated