An Investigator Initiated, Within-Subject, Proof of Concept Study to Assess the Efficacy and Safety of Voltaren Gel in Subjects With DOMS

• Sponsor: Lotus Clinical Research, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT02087748
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 12

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate analgesic efficacy of Topical Voltaren Gel (diclofenac sodium gel) 1% applied QID compared to Placebo in Subjects Experiencing Delayed Onset Muscle Soreness.

Condition or Disease	Intervention/Treatment	Phase
Pain; Delayed Onset Muscle Soreness	Drug: 1% diclofenac sodium gel; Drug: Placebo	Phase 4

Detailed Description

The purpose of this randomized, double-blind, placebo controlled, within-subject study is to evaluate the efficacy of topical diclofenac sodium gel (DSG) 1% in reducing pain associated with delayed onset muscle soreness (DOMS). Following exercise, subjects reporting significant DOMS received topical DSG 1% applied to 1 leg and placebo applied to the other every 6 hours for 48 hours.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Within-Subject, Proof of Concept Study to Assess the Analgesic Efficacy and Safety of Voltaren Gel (1% Diclofenac Sodium) Compared to Placebo in Subjects Experiencing Delayed Onset Muscle Soreness
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1% diclofenac sodium gel Diclofenac sodium 1% gel 4 grams applied topically Q6 hour for 48 hours	Drug: 1% diclofenac sodium gel; Diclofenac sodium 1% gel 4 grams applied topically Q6 hour for 48 hours; Other Names: Voltaren
Placebo Comparator: Placebo Placebo gel 4gm applied topically Q6 hour for 48 hours	Drug: Placebo; Placebo gel 4gm applied topically Q6 hour for 48 hours; Other Names: Matching placebo

Outcome Measures

Primary Outcome Measures

1. Mean Reduction in SPID Scores of DOMS on Walking Over 24 Hours [7 days]

   The primary outcome is the analgesic efficacy of Topical Voltaren® gel compared to placebo in the reduction of the pain associated with DOMS. The statistical comparison of interest will be the mean reduction in DOMS scores upon walking in the leg receiving Topical Voltaren® gel vs the leg receiving placebo over the first 24 hours post treatment. Pain intensity was assessed at predefined time points (Predose, 3, 9, 15, 21, and 24 hours after first drug administration) using an 11-point Numeric Rating Scale (NPRS) where a score of zero indicates "no pain" and "10" indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NPRS values - baseline NPRS values) were analyzed. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -50 (indicative of an increase in pain) to 50 (indicative of a decrease in pain).

Secondary Outcome Measures

1. Mean Reduction in SPID Scores of DOMS at Rest Over 24 Hours [7 days]

   The secondary outcome is the mean reduction in DOMS scores at rest in the leg receiving Topical Voltaren® gel versus the leg receiving placebo over the first 24 hours post treatment initiation. Pain intensity was assessed at predefined time points (at Predose, 3, 9, 15, 21, and 24 hours after first drug administration) using an 11-point Numeric Rating Scale (NPRS) where a score of zero indicates "no pain" and a score of 10 indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NPRS values - baseline NPRS values) were analyzed. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -50 (indicative of an increase in pain) to 50 (indicative of a decrease in pain).

2. Mean Reduction in SPID Scores of DOMS While Standing Over 24 Hours [7 days]

   The secondary outcome is the mean reduction in DOMS scores while standing in the leg receiving Topical Voltaren® gel versus the leg receiving placebo over the first 24 hours post treatment initiation. Pain intensity was assessed at predefined time points (at Predose, 3, 9, 15, 21, and 24 hours after first drug administration) using an 11-point Numeric Rating Scale (NPRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NPRS values - baseline NPRS values) were analyzed. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -50 (indicative of an increase in pain) to 50 (indicative of a decrease in pain).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Patients who provide written informed consent prior to enrollment

• Male or female and 18 to 35 years of age.

• Patients who are not engaged in regular lower extremity fitness activities for more than 2 times per week for ≥2 consecutive weeks in the past 6 months prior to screening.

• Female patients are eligible only if all of the following apply:

• Not pregnant (subjects of child bearing potential must have a negative beta human chorionic gonadotropin (β-hCG) pregnancy test at screening);

• Not lactating;

• Not planning to become pregnant within the duration of the study;

• Patients who are willing and capable of understanding and cooperating with the requirements of the study.

• Patients able to understand and communicate in English.

Randomization Inclusion Criteria:

• Patients who report a DOMS score ≥4 at rest (numerical rating scale of 0 to 10, where 0 is no pain and 10 is worst pain imaginable) secondary to delayed muscle soreness on both right and left legs. The DOMS scores at rest reported for each leg must be within 3 points of each other.

• Patients must report a categorical pain rating of moderate to severe for each leg on a scale of none, mild, moderate, or severe prior to randomization.

Exclusion Criteria:

• Have a body mass index of >32 kg/m2

• History of active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration or bleeding within 30 days preceding screening.

• Psychiatric disease including major depression, bipolar disorder, or anxiety, or other medical condition that, in the opinion of the Investigator, would interfere with the evaluation of study drug efficacy or safety

• History of clinically significant cardiovascular, cerebrovascular, metabolic, pulmonary, neurological, hematological, autoimmune, psychiatric or endocrine disorders, including individuals with Type I or Type II diabetes, or other clinically significant medical condition that, in the opinion of the Investigator, may preclude safe study participation.

• Have had surgery or scheduled to undergo surgery of the hips or knees within 6 months prior to screening and/or during the study participation.

• Have significant biomechanical abnormality in the lower extremity that would preclude study evaluations, such as: peripheral or central neurological disease, significant back pain; symptomatic osteoarthritis of the hips, knew, or feet, or other painful conditions of the lower extremities.

• Have any type of orthopedic and/or prosthetic device or any skin abnormalities on the legs that may interfere with local tolerability.

• Currently taking corticosteroids or topical analgesic or anti inflammatory treatment whose the duration of action may affect study evaluations.

• Malignancy in the last 5 years, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin that has been surgically cured, or any Stage 1 cancer or carcinoma in situ cured by resection or localized radiation at least 5 years prior to screening with no evidence of recurrence.

• History of allergy (cutaneous or systemic), hypersensitivity, or asthma to any of the following: diclofenac, paracetamol, acetylsalicylic acid, salicylic acid, other NSAID or cyclooxygenase 2-specific inhibitor (COXIB) or known intolerance (cutaneous or systemic) to any of the ingredients in the gel, such as isopropyl alcohol or propylene glycol.

• History of known narcotic, analgesic, or alcohol abuse.

• Any cognitive impairment that would, in the opinion of the Investigator, preclude study participation or compliance with study procedures (e.g., Alzheimer's dementia).

• Previously received an investigational product within 30 days before the scheduled dose of study medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lotus Clinical Research, LLC	Pasadena	California	United States	91105

Sponsors and Collaborators

• Lotus Clinical Research, LLC
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Neil Singla, MD, Lotus Clinical Research, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Neil Singla, Principal Investigator, Lotus Clinical Research, LLC
• ClinicalTrials.gov Identifier: NCT02087748
• Other Study ID Numbers: LCR-VOL-01C
• First Posted: Mar 14, 2014
• Last Update Posted: Dec 10, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Neil Singla, Principal Investigator, Lotus Clinical Research, LLC: DOMS
• Additional relevant MeSH terms: Myalgia; Diclofenac

Study Results

Participant Flow

Recruitment Details	Dates of recruitment period: First subject was enrolled in March 2014 and the last subject was enrolled in April 2014. Types of location: Investigative site was located at one research center.

Arm/Group Title	1% Diclofenac Sodium Gel
Arm/Group Description	Diclofenac sodium 1% gel 4 grams applied topically Q6 hours for 48 hours to one leg, and placebo to the other leg.
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	1% Diclofenac Sodium Gel
Arm/Group Description	Diclofenac sodium 1% gel 4 grams applied topically Q6 hours for 48 hours to one leg, and placebo to the other leg.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.0 (3.58)
Sex: Female, Male (Count of Participants)
Female	9 37.5%
Male	15 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 29.2%
Not Hispanic or Latino	17 70.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	9 37.5%
White	13 54.2%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Mean Reduction in SPID Scores of DOMS on Walking Over 24 Hours
Description	The primary outcome is the analgesic efficacy of Topical Voltaren® gel compared to placebo in the reduction of the pain associated with DOMS. The statistical comparison of interest will be the mean reduction in DOMS scores upon walking in the leg receiving Topical Voltaren® gel vs the leg receiving placebo over the first 24 hours post treatment. Pain intensity was assessed at predefined time points (Predose, 3, 9, 15, 21, and 24 hours after first drug administration) using an 11-point Numeric Rating Scale (NPRS) where a score of zero indicates "no pain" and "10" indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NPRS values - baseline NPRS values) were analyzed. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -50 (indicative of an increase in pain) to 50 (indicative of a decrease in pain).
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1% Diclofenac Sodium Gel	Placebo
Arm/Group Description	Diclofenac sodium 1% gel 4 grams applied topically Q6 hours for 48 hours 1% diclofenac sodium gel	Placebo gel 4gm applied topically Q6H for 48 hours Placebo: gel manufactured to mimic Diclofenac sodium1% gel
Measure Participants	24	24
Mean (Standard Deviation) [units on a scale]	34.87 (22.86)	23.62 (19.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1% Diclofenac Sodium Gel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0324
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Mean Reduction in SPID Scores of DOMS at Rest Over 24 Hours
Description	The secondary outcome is the mean reduction in DOMS scores at rest in the leg receiving Topical Voltaren® gel versus the leg receiving placebo over the first 24 hours post treatment initiation. Pain intensity was assessed at predefined time points (at Predose, 3, 9, 15, 21, and 24 hours after first drug administration) using an 11-point Numeric Rating Scale (NPRS) where a score of zero indicates "no pain" and a score of 10 indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NPRS values - baseline NPRS values) were analyzed. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -50 (indicative of an increase in pain) to 50 (indicative of a decrease in pain).
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1% Diclofenac Sodium Gel	Placebo
Arm/Group Description	Diclofenac sodium 1% gel 4 grams applied topically Q6 hour for 48 hours 1% diclofenac sodium gel: Diclofenac sodium 1% gel 4 grams applied topically Q6 hour for 48 hours	Placebo gel 4gm applied topically Q6 hour for 48 hours Placebo: Placebo gel 4gm applied topically Q6 hour for 48 hours
Measure Participants	24	24
Mean (Standard Deviation) [units on a scale]	28.06 (23.84)	24.81 (20.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1% Diclofenac Sodium Gel, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3688
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Mean Reduction in SPID Scores of DOMS While Standing Over 24 Hours
Description	The secondary outcome is the mean reduction in DOMS scores while standing in the leg receiving Topical Voltaren® gel versus the leg receiving placebo over the first 24 hours post treatment initiation. Pain intensity was assessed at predefined time points (at Predose, 3, 9, 15, 21, and 24 hours after first drug administration) using an 11-point Numeric Rating Scale (NPRS) where a score of zero indicates "no pain" and a score of ten indicates "pain as bad as you can imagine". Pain Intensity Differences at each predefined time point (calculated as post-baseline NPRS values - baseline NPRS values) were analyzed. The theoretical maximum range of Sum of pain intensity differences (SPID24) is from -50 (indicative of an increase in pain) to 50 (indicative of a decrease in pain).
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	1% Diclofenac Sodium Gel	Placebo
Arm/Group Description	Diclofenac sodium 1% gel 4 grams applied topically Q6 hour for 48 hours 1% diclofenac sodium gel: Diclofenac sodium 1% gel 4 grams applied topically Q6 hour for 48 hours	Placebo gel 4gm applied topically Q6 hour for 48 hours Placebo: Placebo gel 4gm applied topically Q6 hour for 48 hours
Measure Participants	24	24
Mean (Standard Deviation) [units on a scale]	33.9 (23.29)	21.62 (18.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	1% Diclofenac Sodium Gel, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0275
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Adverse Event Reporting Description	For serious adverse events, events will be collected when identified from the date Subject signed Informed Consent up to 30 days after discontinuation from the study. For other adverse events, events will be collected until study completion or early termination.
Arm/Group Title	1% Diclofenac Sodium Gel		Placebo
Arm/Group Description	Diclofenac sodium 1% gel 4 grams applied topically Q6 hours for 48 hours 1% diclofenac sodium gel		Placebo gel 4gm applied topically Q6H for 48 hours Placebo: gel manufactured to mimic Diclofenac sodium1% gel
All Cause Mortality
	1% Diclofenac Sodium Gel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	1% Diclofenac Sodium Gel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	1% Diclofenac Sodium Gel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.