AMZ001 for the Treatment of Knee Osteoarthritis Symptoms

• Sponsor: Amzell (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03691844
• Collaborator: (none)
• Enrollment: 444
• Locations: 7
• Arms: 4
• Actual Duration (Months): 9.1
• Patients Per Site: 63.4
• Patients Per Site Per Month: 6.9

Study Details

Study Description

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee	Drug: AMZ001; Drug: Placebo; Drug: Comparator	Phase 2/Phase 3

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily. Participants will be evaluated for osteoarthritis by X-ray images of the knees and one knee will be selected for treatment as the target knee. The study gel will be applied directly to that knee throughout the 4 weeks of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 444 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: placebo-controlled, double-blind, randomized, parallel studyplacebo-controlled, double-blind, randomized, parallel study
• Masking: Double (Participant, Investigator)
• Masking Description: 3 treatment arms will be double-blind, the 4th (comparator) will be single-blind
• Primary Purpose: Treatment
• Official Title: A Placebo-controlled, Double-blind, Randomized, Trial of AMZ001 for the Treatment of Knee Osteoarthritis Symptoms
• Actual Study Start Date: Oct 4, 2018
• Actual Primary Completion Date: Jul 9, 2019
• Actual Study Completion Date: Jul 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMZ001 + Placebo on the target knee	Drug: AMZ001; diclofenac gel
Experimental: AMZ001 on the target knee	Drug: AMZ001; diclofenac gel
Placebo Comparator: Placebo on the target knee	Drug: Placebo; Placebo
Active Comparator: Comparator Diclofenac gel on the target knee	Drug: Comparator; diclofenac gel; Other Names: active comparator

Outcome Measures

Primary Outcome Measures

1. WOMAC Pain Sub-score [baseline, week 4]

   Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.

Secondary Outcome Measures

1. WOMAC Total Score and WOMAC Function and Stiffness [baseline, week 4]

   Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20). The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.

2. WOMAC Pain Weight-bearing Score and Non-weight-bearing Score [baseline, week 4]

   Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.

3. ICOAP Scores [baseline, week 4]

   Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]). ICOAP scores were normalized to a 0-100 point scale, where 0 is no pain and higher scores indicate greater pain.

4. Physical Function [baseline, week 4]

   Change in baseline in physical function assessed by the chair-stand test. The test measures the maximum number of chair stand repetitions possible in a 30-second period with out using the arms. Where 0 is no repetition completed and higher numbers corresponds to greater repetitions and physical function.

5. Proportion of Responders as Per OMERACT-OARSI Criteria [week 4]

   Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI) response involves changes that are deemed to be clinically relevant in three domains: pain, function, and PGA (Patient Global Assessment). For each of these domains, ranges are defined for absolute and percent changes from baseline that correspond to "high improvement" and "moderate improvement". OMERACT-OARSI response is defined as either high improvement in at least 1 of WOMAC pain and function scores OR moderate improvement in at least 2 of WOMAC pain scores, WOMAC function score or Patient Global Assessment (PGA)

6. Total Dose of Rescue Medication [weeks 1 through 4]

   Total dose of rescue medication calculated as the average gram use/day, based on pill counts.

7. Time Between Baseline and First Use of Rescue Medication [weeks 1 through 4]

   Time between baseline and first use of rescue medication.

8. WOMAC Pain Sub-score (Dose Comparison) [baseline, week 4]

   Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.

9. ICOAP Scores (Dose Comparison) [baseline, week 4]

   Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]). ICOAP scores were normalized to a 0-100 point scale, where 0 is no pain and higher scores indicate greater pain.

10. WOMAC Pain Weight-bearing Score and Non-weight-bearing Score (Dose Comparison) [baseline, week 4]

    Changes from baseline in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.

11. Physical Function (Dose Comparison) [baseline, week 4]

    Change in baseline assessed by the chair-stand test. The test measures the maximum number of chair stand repetitions possible in a 30-second period with out using the arms. Where 0 is no repetition completed and higher numbers corresponds to greater repetitions and physical function.

12. WOMAC Total Score and WOMAC Function and Stiffness (Dose Comparison) [baseline, week 4]

    Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20). The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.

13. Impact of Osteoarthritis on Daily Living (PGA Score) [baseline, week 4]

    Change from baseline in Impact of OA daily living assessed using Patient Global Assessment (PGA) score. PGA is scored on a 11-point scale from 0 (none) to 10 (extreme), where higher scores represents a higher level of disease activity or worse health.

14. Work Productivity [baseline, week 4]

    Change from baseline in work productivity and activity assessed by the Work Productivity and Active Impairment (WPAI scores 0-100% in four different categories: absenteeism, presenteeism, work productivity loss, and activity impairment). Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.

15. Change in Quality of Life: EQ5D VAS Score [baseline, week 4]

    The EuroQol-5 Domain (EQ-5D) is a standardized generic measure of health-related quality of life. The visual analog scale (VAS) is scored on a 0-100 scale, where 0 is "the worst health you can imagine" and 100, "the best health you can imagine".

Other Outcome Measures

1. Safety Endpoint (Adverse Events) [weeks 1 through 4]

   Nature, incidence and severity of AEs.

2. Skin Tolerability Assessment (Skin Reactions) [week 4]

   Skin tolerability assessment, incidence of erythema at the application site. Grading scheme from 0-4 (0, normal skin, no erythema; 4, blister formation and/or necrosis).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and X-ray criteria.

2. Pain score rated on an 11-point numerical rating scale of the target knee of ≥ 20 and ≤ 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening, after washout of any pain relief medication.

3. Women of child-bearing potential must use at least an acceptably effective method of contraception from enrollment up to at least 3 months after the study end.

4. Knee pain in the target knee for 14 days of the preceding month (knee pain due to osteoarthritis and not due to another condition such as bursitis, tendinitis, etc.) based on subject report.

5. On stable pain therapy (i.e., at least 3 days per week for the previous month) with an oral or topical NSAID prescribed by physician for 30 days prior to the Screening Visit and/or prescribed over-the-counter.

6. Except for osteoarthritis, in reasonably good health as determined by the Investigator.

Exclusion Criteria:

1. Known or suspected hypersensitivity to diclofenac, other non-steroidal anti-inflammatory drugs or related substances including aspirin, any of the components in either of the investigation products, or any physical impediment to gel application on the target knee.

2. Injection of corticosteroids or hyaluronic acid in the target knee within 6 months of screening or into any other joint within 30 days of screening.

3. High dose oral/injected corticosteroid treatment of more than 14 days during the past 6 months prior to screening.

4. Major surgery or arthroscopy of the target knee within the previous year prior to screening.

5. Planned surgery of the target knee within the next 3 months.

6. Presence of an additional non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or pseudo-gout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug.

7. Medical history of coronary artery bypass graft surgery.

8. Current cancer or treatment for cancer within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area.

9. Secondary osteoarthritis of the target knee, previous procedures or trauma affecting joint of the target knee.

10. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in hip(s) exceeds that of the target knee using the WOMAC Hip Pain subscore, presence of significant back pain, or at least one migraine attack within the past 12 months before screening, as reported by the subject.

11. Body Mass Index > 45.0 kg/m2.

12. Generalized skin irritation, previous skin reactions upon use of topical NSAIDs, current skin irritation or redness at the planned site of gel application, or significant skin disease including psoriasis, as judged by the investigator.

13. Known presence of a ulcer or any gastrointestinal bleeding within 6 months prior to screening.

14. Use of moderate or higher doses of opioid medication for the treatment of pain within 6 weeks before the screening visit.

15. Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the screening visit.

16. History of alcohol or drug abuse within the past year prior to randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Consulting	Milford	Connecticut	United States	06460
2	Premier Medical Associates	The Villages	Florida	United States	32162
3	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
4	CCR Brno, s.r.o	Brno		Czechia
5	CCR Czech, a.s	Pardubice		Czechia
6	CCR Prague s.r.o.	Praha		Czechia
7	Sanos Clinic	Herlev		Denmark

Sponsors and Collaborators

• Amzell

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Aug 5, 2019
• Study Protocol - Nov 22, 2018

More Information

Publications

None provided.

• Responsible Party: Amzell
• ClinicalTrials.gov Identifier: NCT03691844
• Other Study ID Numbers: AMZ001-006
• First Posted: Oct 2, 2018
• Last Update Posted: Oct 6, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Amzell: AMZ001
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

Participant Flow

Recruitment Details	Seven trial sites in Denmark (1 site), Czech Republic (3 sites) and the USA (3 sites). Trial initiation: 04-Oct-2018 Trial completion: 09-Jul-2019

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID	Voltaren 1% QID
Arm/Group Description	on the target knee AMZ001 gel twice daily. BID: Twice a day	on the target knee AMZ001 gel once daily, Placebo gel once daily. QD: Every day/daily	on the target knee Placebo gel twice daily. BID: twice a day/ twice daily	on the target knee Voltaren gel 1% applied 4 times a day QID: 4 times every day
Period Title: Overall Study
STARTED	121	121	121	81
COMPLETED	114	109	108	70
NOT COMPLETED	7	12	13	11

Baseline Characteristics

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID	Voltaren 1% QID	Total
Arm/Group Description	on the target knee AMZ001 gel twice daily. BID: twice a day/twice daily	on the target knee AMZ001 gel once daily, Placebo gel once daily. QD: Every day/daily	on the target knee Placebo gel twice daily. BID: 2 times a day/ twice a day	on the target knee Voltaren gel 1% applied 4 times a day	Total of all reporting groups
Overall Participants	121	121	121	81	444
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	60 49.6%	55 45.5%	62 51.2%	39 48.1%	216 48.6%
>=65 years	61 50.4%	66 54.5%	59 48.8%	42 51.9%	228 51.4%
Sex: Female, Male (Count of Participants)
Female	83 68.6%	83 68.6%	77 63.6%	54 66.7%	297 66.9%
Male	38 31.4%	38 31.4%	44 36.4%	27 33.3%	147 33.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 0.8%	0 0%	3 2.5%	1 1.2%	5 1.1%
Not Hispanic or Latino	120 99.2%	121 100%	118 97.5%	80 98.8%	439 98.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	1 0.8%	2 1.7%	0 0%	3 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 1.2%	1 0.2%
Black or African American	6 5%	1 0.8%	4 3.3%	3 3.7%	14 3.2%
White	115 95%	119 98.3%	115 95%	77 95.1%	426 95.9%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Baseline WOMAC pain sub-score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	28.2 (6.07)	27.5 (5.24)	27.1 (4.82)	27.3 (5.48)	27.5 (5.41)

Outcome Measures

1. Primary Outcome

Title	WOMAC Pain Sub-score
Description	Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	AMZ001 gel twice daily	on the target knee AMZ001 gel once daily, Placebo gel once daily.	Placebo gel twice daily
Measure Participants	120	120	120
Least Squares Mean (95% Confidence Interval) [score on a scale]	-26.49	-27.33	-22.73

2. Secondary Outcome

Title	WOMAC Total Score and WOMAC Function and Stiffness
Description	Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20). The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Change from baseline WOMAC total score	-24.15	-23.32	-20.57
Change from baseline WOMAC function score	-23.43	-22.30	-19.94
Change from baseline WOMAC stiffness score	-23.17	-23.35	-20.65

3. Secondary Outcome

Title	WOMAC Pain Weight-bearing Score and Non-weight-bearing Score
Description	Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Change from baseline WOMAC pain weight bearing	-27.03	-27.68	-22.65
Change from baseline WOMAC pain non-weight bearing	-25.65	-26.89	-22.93

4. Secondary Outcome

Title	ICOAP Scores
Description	Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]). ICOAP scores were normalized to a 0-100 point scale, where 0 is no pain and higher scores indicate greater pain.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
ICOAP total score	-20.62	-18.87	-17.98
ICOAP constant pain score	-20.82	-19.01	-18.37
ICOAP intermittent pain score	-20.18	-19.00	-17.99

5. Secondary Outcome

Title	Physical Function
Description	Change in baseline in physical function assessed by the chair-stand test. The test measures the maximum number of chair stand repetitions possible in a 30-second period with out using the arms. Where 0 is no repetition completed and higher numbers corresponds to greater repetitions and physical function.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Least Squares Mean (95% Confidence Interval) [repetitions]	2.41	2.30	2.37

6. Secondary Outcome

Title	Proportion of Responders as Per OMERACT-OARSI Criteria
Description	Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI) response involves changes that are deemed to be clinically relevant in three domains: pain, function, and PGA (Patient Global Assessment). For each of these domains, ranges are defined for absolute and percent changes from baseline that correspond to "high improvement" and "moderate improvement". OMERACT-OARSI response is defined as either high improvement in at least 1 of WOMAC pain and function scores OR moderate improvement in at least 2 of WOMAC pain scores, WOMAC function score or Patient Global Assessment (PGA)
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	115	109	109
Number (95% Confidence Interval) [Proportion of responders]	0.765	0.826	0.725

7. Secondary Outcome

Title	Total Dose of Rescue Medication
Description	Total dose of rescue medication calculated as the average gram use/day, based on pill counts.
Time Frame	weeks 1 through 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Least Squares Mean (95% Confidence Interval) [gram/day]	0.27	0.31	0.30

8. Secondary Outcome

Title	Time Between Baseline and First Use of Rescue Medication
Description	Time between baseline and first use of rescue medication.
Time Frame	weeks 1 through 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Median (95% Confidence Interval) [Days]	17	9	10

9. Secondary Outcome

Title	WOMAC Pain Sub-score (Dose Comparison)
Description	Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.
Measure Participants	120	120
Least Squares Mean (95% Confidence Interval) [score on a scale]	-26.49	-27.33

10. Secondary Outcome

Title	ICOAP Scores (Dose Comparison)
Description	Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]). ICOAP scores were normalized to a 0-100 point scale, where 0 is no pain and higher scores indicate greater pain.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.
Measure Participants	120	120
Least Squares Mean (95% Confidence Interval) [score on a scale]	-20.62	-18.87

11. Secondary Outcome

Title	WOMAC Pain Weight-bearing Score and Non-weight-bearing Score (Dose Comparison)
Description	Changes from baseline in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.
Measure Participants	120	120
Weight-bearing	-27.03	-27.68
Non-weight-bearing	-25.65	-26.89

12. Secondary Outcome

Title	Physical Function (Dose Comparison)
Description	Change in baseline assessed by the chair-stand test. The test measures the maximum number of chair stand repetitions possible in a 30-second period with out using the arms. Where 0 is no repetition completed and higher numbers corresponds to greater repetitions and physical function.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.
Measure Participants	120	120
Least Squares Mean (95% Confidence Interval) [repetitions]	2.41	2.3

13. Secondary Outcome

Title	WOMAC Total Score and WOMAC Function and Stiffness (Dose Comparison)
Description	Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20). The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.
Measure Participants	120	120
Function	-23.43	-22.30
Stiffness	-23.17	-23.35

14. Secondary Outcome

Title	Impact of Osteoarthritis on Daily Living (PGA Score)
Description	Change from baseline in Impact of OA daily living assessed using Patient Global Assessment (PGA) score. PGA is scored on a 11-point scale from 0 (none) to 10 (extreme), where higher scores represents a higher level of disease activity or worse health.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Least Squares Mean (95% Confidence Interval) [score on a scale]	-2.29	-2.31	-1.68

15. Secondary Outcome

Title	Work Productivity
Description	Change from baseline in work productivity and activity assessed by the Work Productivity and Active Impairment (WPAI scores 0-100% in four different categories: absenteeism, presenteeism, work productivity loss, and activity impairment). Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	45	41	39
WPAI % Time missed	0.39	-3.10	1.58
WPAI % Impairment while working	-13.11	-14.38	-5.28
WPAI % Overall work impairment	-11.69	-16.93	-6.50
WPAI % Activity impairment	-17.75	-20.41	-13.03

16. Secondary Outcome

Title	Change in Quality of Life: EQ5D VAS Score
Description	The EuroQol-5 Domain (EQ-5D) is a standardized generic measure of health-related quality of life. The visual analog scale (VAS) is scored on a 0-100 scale, where 0 is "the worst health you can imagine" and 100, "the best health you can imagine".
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

The mITT (modified Intent to treat; N=120) population set includes subjects with a baseline and at least one post-treatment WOMAC pain sub-score and was used in statistical analysis for primary and secondary endpoint outcome measures.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	120	120	120
Least Squares Mean (95% Confidence Interval) [score on a scale]	13.04	11.76	8.34

17. Other Pre-specified Outcome

Title	Safety Endpoint (Adverse Events)
Description	Nature, incidence and severity of AEs.
Time Frame	weeks 1 through 4

Outcome Measure Data

Analysis Population Description

The SAF (Safety Analysis Set; N=121) was used for safety evaluation of adverse events.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID	Voltaren 1% QID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.	on the target knee Voltaren gel 1% applied 4 times a day QID: 4 times every day
Measure Participants	121	121	121	81
All TEAEs	51 42.1%	53 43.8%	75 62%	26 32.1%
Deaths	0 0%	0 0%	0 0%	0 0%
SAEs	0 0%	0 0%	0 0%	0 0%
AEs leading to treatment discontinuation	3 2.5%	8 6.6%	7 5.8%	5 6.2%
ADR	29 24%	29 24%	51 42.1%	9 11.1%
Severity Mild	39 32.2%	45 37.2%	66 54.5%	20 24.7%
Severity Moderate	17 14%	11 9.1%	14 11.6%	9 11.1%
Severity Severe	0 0%	0 0%	1 0.8%	1 1.2%

18. Other Pre-specified Outcome

Title	Skin Tolerability Assessment (Skin Reactions)
Description	Skin tolerability assessment, incidence of erythema at the application site. Grading scheme from 0-4 (0, normal skin, no erythema; 4, blister formation and/or necrosis).
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

Nature, incidence and severity of AEs. The SAF (Safety Analysis Set; N=121) was used for safety evaluation of adverse events.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID	Voltaren 1% QID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.	on the target knee Voltaren gel 1% applied 4 times a day QID: 4 times every day
Measure Participants	121	121	121	81
Normal skin; no erythema	100 82.6%	89 73.6%	79 65.3%	68 84%
Questionable erythema not covering entire app site	14 11.6%	18 14.9%	20 16.5%	3 3.7%
Definite erythema not covering entire app site	2 1.7%	2 1.7%	10 8.3%	0 0%
Definite erythema and swelling or induration	0 0%	0 0%	0 0%	0 0%
Blister formation and/or necrosis	0 0%	0 0%	0 0%	1 1.2%

19. Post-Hoc Outcome

Title	WOMAC Pain Sub-score (Subgroup With WOMAC Normalized Pain Sub-score ≥40 at Baseline)
Description	Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

Post-hoc statistical analyses were performed for the comparison of each of the AMZ001 regimens vs placebo and between the two AMZ001 regimens. Sub-group of subjects meeting the WOMAC pain sub-score inclusion criterion at both screening and baseline.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	109	107	106
Least Squares Mean (95% Confidence Interval) [score on a scale]	-28.54	-29.02	-23.18

20. Post-Hoc Outcome

Title	WOMAC Total Score and WOMAC Function and Stiffness (Subgroup With WOMAC Normalized Pain Sub-score ≥40 at Baseline)
Description	Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20) . The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks.
Time Frame	baseline, week 4

Outcome Measure Data

Analysis Population Description

Post-hoc statistical analyses were performed for the comparison of each of the AMZ001 regimens vs placebo and between the two AMZ001 regimens. Sub-group of subjects meeting the WOMAC pain sub-score inclusion criterion at both screening and baseline.

Arm/Group Title	AMZ001 BID	AMZ001 + Placebo QD	Placebo BID
Arm/Group Description	on the target knee AMZ001 gel twice daily.	on the target knee AMZ001 gel once daily, Placebo gel once daily.	on the target knee Placebo gel twice daily.
Measure Participants	109	107	106
Change from baseline WOMAC total score	-25.54	-24.03	-20.61
Change from baseline WOMAC function score	-24.69	-22.84	-19.84
Change from baseline WOMAC stiffness score	-24.08	-23.57	-20.33

Adverse Events

Time Frame	4 Weeks
Arm/Group Title	AMZ001 BID		AMZ001 + Placebo QD		Placebo BID		Voltaren 1% QID
Arm/Group Description	AMZ001 gel twice daily		on the target knee AMZ001 gel once daily, Placebo gel once daily.		Placebo gel twice daily		on the target knee Voltaren gel 1% applied 4 times a day
All Cause Mortality
	AMZ001 BID		AMZ001 + Placebo QD		Placebo BID		Voltaren 1% QID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/121 (0%)		0/121 (0%)		0/121 (0%)		0/121 (0%)
Serious Adverse Events
	AMZ001 BID		AMZ001 + Placebo QD		Placebo BID		Voltaren 1% QID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/121 (0%)		0/121 (0%)		0/121 (0%)		0/121 (0%)
Other (Not Including Serious) Adverse Events
	AMZ001 BID		AMZ001 + Placebo QD		Placebo BID		Voltaren 1% QID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/121 (24%)		30/121 (24.8%)		52/121 (43%)		11/81 (13.6%)
General disorders
Application Site erythema	11/121 (9.1%)	12	15/121 (12.4%)	16	40/121 (33.1%)	41	4/81 (4.9%)	4
Application site dryness	18/121 (14.9%)	18	13/121 (10.7%)	13	16/121 (13.2%)	16	5/81 (6.2%)	5
Application site pruritus	5/121 (4.1%)	5	8/121 (6.6%)	8	6/121 (5%)	6	2/81 (2.5%)	3
Infections and infestations
Nasopharyngitis	6/121 (5%)	7	3/121 (2.5%)	3	6/121 (5%)	6	4/81 (4.9%)	5
Nervous system disorders
Headache	2/121 (1.7%)	3	1/121 (0.8%)	2	8/121 (6.6%)	9	0/81 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.