A Clinical Endpoint Bioequivalence Study of "Oxymetazoline Hydrochloride Cream"

• Sponsor: Actavis Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03954444
• Collaborator: Teva Pharmaceuticals USA (Industry)
• Enrollment: 1,105
• Location: 1
• Arms: 3
• Actual Duration (Months): 10.4
• Patients Per Site Per Month: 105.8

Study Details

Study Description

Brief Summary

A Randomized, Double-blind, Parallel-group, Three-arm, Placebo-controlled, Multi-Site Therapeutic Equivalence Study with Clinical End-points Comparing Test Product "Oxymetazoline hydrochloride Cream, 1%" to Reference Product "RHOFADE™ Cream, 1%" in the Treatment of Moderate to Severe Persistent Facial Erythema of Rosacea

Condition or Disease	Intervention/Treatment	Phase
Rosacea	Drug: Oxymetazoline Hydrochloride; Drug: Rhofade Cream, 1%; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1105 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Parallel Group, Three Arm, Placebo Controlled, Multi-Site Therapeutic Equivalence Study With Clinical End-points Comparing Test Product "Oxymetazoline Hydrochloride Cream, 1%" to Reference Product "RHOFADETM Cream, 1%" in the Treatment of Moderate to Severe Persistent Facial Erythema of Rosacea
• Actual Study Start Date: Apr 15, 2019
• Actual Primary Completion Date: Jan 7, 2020
• Actual Study Completion Date: Feb 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oxymetazoline hydrochloride Cream, 1% Oxymetazoline hydrochloride cream, 1%	Drug: Oxymetazoline Hydrochloride; Test Comparator
Active Comparator: RHOFADE Cream, 1% RHOFADE Cream, 1%	Drug: Rhofade Cream, 1%; Reference Comparator; Other Names: Oxymetazoline hydrochloride
Placebo Comparator: Vehicle Cream Vehicle cream	Drug: Placebo; Placebo Comparator; Other Names: Oxymetazoline hydrochloride

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Treatment Success at All Time Points 3, 6, 9 and 12 Hours Post-application on Day 29. Treatment Success Was Defined as Having a Clinician Erythema Assessment Score at Least 2 Grades Lower Than the Baseline (Day 1 Predose) Value [29 days]

   The primary efficacy endpoint was the proportion of subjects with treatment success at all time points 3, 6, 9, and 12 hours post-application on Day 29. Treatment success was defined as having CEA score at least 2 grades lower than the baseline (Day 1 pre-dose) value. Clinician Erythema Assessment was measured as (0-clear, 1-almost clear, 2-mild, 3-moderate, 4- severe).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• (1) Study subjects must have provided IRB approved written informed consent using the latest version of the IRB informed consent form, (or assent in applicable states/countries). In addition, study subjects must sign a HIPAA authorization, if applicable.

• (2) Healthy male or non-pregnant females, ≥18 years-of-age with a clinical diagnosis of rosacea with persistent (non-transient) facial erythema.

• (3) Ability to follow study instructions and complete subject diary without assistance.

• (4) Females of child bearing potential must not be pregnant or lactating at screening visit and at baseline visit, as documented by a negative urine pregnancy test.

• (5) Female subjects of childbearing potential must be willing to use an acceptable form of birth control from the day of the first dose administration to 30 days after the last administration of Investigational Product (IP). A sterile sexual partner is NOT considered an adequate form of birth control.

• (6) Moderate to severe persistent facial erythema associated with rosacea, defined as a grade of ≥3 on the CEA scale as assessed by the Investigator at Screening and on Baseline (Day 1) visit prior to study drug application.

• (7) Moderate to severe persistent facial erythema associated with rosacea, defined as a grade of ≥3 on the SSA scale as assessed by the subject at Screening and on Baseline (Day 1) visit prior to study drug application.

• (8) Stable erythema (for at least 3 months prior to screening) associated with rosacea, with minimal variation from day to day and within each day, in the opinion of the subject.

• (9) Willingness to complete the required visits including short stay for at least 12 hours at the investigational site for 2 separate visits.

• (10) Subjects who use make-up, facial moisturizers, creams, lotions, cleansers and/or sunscreens must have used the same product brands/types for a minimum period of 4 weeks prior to Baseline, must agree not to change brand/type or frequency of use throughout the study and must agree not to use make-up, facial moisturizers, creams, lotions and/or sunscreens on the scheduled clinic visit day before the visit.

• (11) Subject must be willing to avoid the use of abrasive cleansers or washes (e.g., exfoliating facial scrubs), adhesive cleansing strips (e.g., Bioré® Pore Strips) and wax epilation on the face, during the entire duration of their study participation.

• (12) Subject's willingness to minimize external factors that might trigger rosacea flare-ups (e.g., spicy foods, thermally hot foods and drinks, hot environments, prolonged sun exposure, strong winds, alcoholic beverages).

• (13) Subject must be in good health and free from any systemic or dermatological disorder (other than rosacea) that, in the opinion of the Investigator, will interfere with the study evaluations or increase the risk of AEs.

• (14) Any skin type or race, providing the skin pigmentation will allow discernment of erythema.

Exclusion Criteria:

• (1) Any of the following conditions: severe or unstable or uncontrolled cardiovascular disease, clinically unstable hypertension, orthostatic hypotension, and uncontrolled hypertension or hypotension, cerebral or coronary insufficiency, Raynaud's Syndrome, thromboangiitis obliterans, scleroderma, Sjögren's syndrome, renal or hepatic impairment.

• (2) Subjects with narrow angle glaucoma.

• (3) Females who are pregnant, breast feeding, or planning a pregnancy during the study.

• (4) Females of childbearing potential who do not agree to utilize an adequate form of contraception during their participation in the study.

• (5) Clinical signs of particular forms of rosacea (rosacea conglobata, rosacea fulminans, isolated rhinophyma, isolated pustulosis of the chin) on the face or other concomitant facial dermatoses that are similar to rosacea such as peri-oral dermatitis, demodicidosis, facial keratosis pilaris, seborrheic dermatitis, acute lupus erythematosus, or actinic telangiectasia that may interfere with the study evaluations, in the opinion of the Investigator.

• (6) Presence of ≥3 facial inflammatory lesions of rosacea at screening and baseline.

• (7) Presence of any skin condition on the face that would interfere with the diagnosis or assessment of rosacea, as determined by the Investigator.

• (8) Excessive facial hair (e.g., beards, sideburns, moustaches, etc.) that would interfere with the study treatments or study assessments.

• (9) History of drug or alcohol abuse within 12 months prior to the Screening visit.

• (10 Known hypersensitivity or allergies to any component of the study treatment.

• (11) Use within 12 hours prior to baseline of any topical products including, but not limited to, lotions, creams, ointments, and cosmetics applied to the face (facial cleanser is acceptable).

• (12) Use 1 week prior to baseline of niacin ≥500 mg/day.

• (13) Use within 2 weeks prior to baseline of products containing topical corticosteroids, topical retinoids, topical antibiotics, topical anti-inflammatory, topical treatment for rosacea, or topical treatment for acne.

• (14) Use within 4 weeks prior to baseline of topical immunomodulators, systemic antibiotics, systemic corticosteroids, systemic anti-inflammatory agents, systemic treatment for rosacea, or systemic treatment for acne (other than oral retinoids, which require a 6-month washout).

• (15) Undergone 4 weeks prior to baseline any dermatologic or surgical procedure on the face.

• (16) Use within 3 months prior to baseline of any systemic immunomodulators known to have an effect on rosacea.

• (17) Use within 6 months prior to baseline of any oral retinoids (e.g., isotretinoin) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).

• (18) Undergone 6 months prior to baseline any laser, light-source (e.g. intense pulsed light, photodynamic therapy) or other energy-based therapy to the face.

• (19) Exposed to excessive UV radiation within 1 week before Screening visit and/or subject is unwilling to refrain from excessive exposure to UV radiation during the course of the study.

• (20) Current use of monoamine oxidase (MAO) inhibitors, barbiturates, opiates, sedatives, systemic anesthetics, alpha-agonists, cardiac glycosides, beta blockers, other antihypertensive agents, or oxymetazoline (e.g., eye drops, nasal sprays).

• (21) Subject has participated in a clinical trial within 30 days or in a biologics study within 6 months preceding admission of this study.

• (22) Previous participation in this study.

• (23) Inability to communicate well (i.e., language problem, poor mental development, psychiatric illness or poor cerebral function), that may impair the ability to provide written informed consent.

• (24) Subject has any evidence of organ dysfunction, chronic infectious disease, system disorder or has a condition or is in a situation that, in the Investigator's opinion, that may put the subject at significant risk, may confound the study results, or may significantly interferes with the subject's participation in the study.

• (25) Employees or family members of the research center or Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 1	Lynchburg	Virginia	United States	24501

Sponsors and Collaborators

• Actavis Inc.
• Teva Pharmaceuticals USA

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 29, 2020
• Statistical Analysis Plan - Feb 18, 2020

More Information

Publications

None provided.

• Responsible Party: Actavis Inc.
• ClinicalTrials.gov Identifier: NCT03954444
• Other Study ID Numbers: OXY2018-01
• First Posted: May 17, 2019
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Rosacea; Phenylephrine; Oxymetazoline

Study Results

Participant Flow

Arm/Group Title	Oxymetazoline Hydrochloride Cream, 1%	RHOFADE Cream, 1%	Vehicle Cream
Arm/Group Description	Oxymetazoline hydrochloride cream, 1% Oxymetazoline Hydrochloride: Test Comparator Subjects applied once daily to face for 29 days	RHOFADE Cream, 1% Rhofade Cream, 1%: Reference Comparator Subjects applied once daily to face for 29 days	Vehicle cream Placebo: Placebo Comparator Subjects applied once daily to face for 29 days
Period Title: Overall Study
STARTED	379	382	344
COMPLETED	366	366	327
NOT COMPLETED	13	16	17

Baseline Characteristics

Arm/Group Title	Oxymetazoline Hydrochloride Cream, 1%	RHOFADE Cream, 1%	Vehicle Cream	Total
Arm/Group Description	Oxymetazoline hydrochloride cream, 1% Oxymetazoline Hydrochloride: Test Comparator	RHOFADE Cream, 1% Rhofade Cream, 1%: Reference Comparator	Vehicle cream Placebo: Placebo Comparator	Total of all reporting groups
Overall Participants	379	382	344	1105
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.9 (13.87)	46.2 (14.01)	47.2 (14.50)	46.8 (14.11)
Sex: Female, Male (Count of Participants)
Female	282 74.4%	284 74.3%	258 75%	824 74.6%
Male	97 25.6%	98 25.7%	86 25%	281 25.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	202 53.3%	205 53.7%	182 52.9%	589 53.3%
Not Hispanic or Latino	177 46.7%	177 46.3%	162 47.1%	516 46.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.3%	1 0.1%
Asian	1 0.3%	0 0%	2 0.6%	3 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.3%	0 0%	1 0.1%
Black or African American	9 2.4%	2 0.5%	4 1.2%	15 1.4%
White	369 97.4%	377 98.7%	337 98%	1083 98%
More than one race	0 0%	2 0.5%	0 0%	2 0.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Baseline Clinical Erythema Assessment Score (Count of Participants)
0-Clear	0 0%	0 0%	0 0%	0 0%
1-Almost Clear	0 0%	0 0%	0 0%	0 0%
2-Mild	0 0%	0 0%	0 0%	0 0%
3-Moderate	287 75.7%	292 76.4%	273 79.4%	852 77.1%
4-Severe	92 24.3%	90 23.6%	71 20.6%	253 22.9%
Baseline Subject Self-Assessment (Count of Participants)
0-No Sign	0 0%	0 0%	0 0%	0 0%
1-Almost Clear	0 0%	0 0%	0 0%	0 0%
2-Mild	0 0%	0 0%	0 0%	0 0%
3-Moderate	282 74.4%	287 75.1%	261 75.9%	830 75.1%
4-Severe	97 25.6%	95 24.9%	83 24.1%	275 24.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Treatment Success at All Time Points 3, 6, 9 and 12 Hours Post-application on Day 29. Treatment Success Was Defined as Having a Clinician Erythema Assessment Score at Least 2 Grades Lower Than the Baseline (Day 1 Predose) Value
Description	The primary efficacy endpoint was the proportion of subjects with treatment success at all time points 3, 6, 9, and 12 hours post-application on Day 29. Treatment success was defined as having CEA score at least 2 grades lower than the baseline (Day 1 pre-dose) value. Clinician Erythema Assessment was measured as (0-clear, 1-almost clear, 2-mild, 3-moderate, 4- severe).
Time Frame	29 days

Outcome Measure Data

Analysis Population Description

Equivalence Analysis of the Primary Endpoint (Per Protocol Population)

Arm/Group Title	Oxymetazoline Hydrochloride Cream, 1%	RHOFADE Cream, 1%	Vehicle Cream
Arm/Group Description	Oxymetazoline hydrochloride cream, 1% Oxymetazoline Hydrochloride: Test Comparator	RHOFADE Cream, 1% Rhofade Cream, 1%: Reference Comparator	Vehicle cream Placebo: Placebo Comparator
Measure Participants	349	356	316
Success	78 20.6%	70 18.3%	51 14.8%
Failure	271 71.5%	286 74.9%	265 77%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline Hydrochloride Cream, 1%, RHOFADE Cream, 1%
	Comments
	Type of Statistical Test	Equivalence
	Comments	90% Confidence Interval, should be within -20% to +20%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.7
	Confidence Interval	(2-Sided) 90%; -2.6 to 8.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oxymetazoline Hydrochloride Cream, 1%, Vehicle Cream
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RHOFADE Cream, 1%, Vehicle Cream
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1126
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	2 month adverse event data collection
Arm/Group Title	Oxymetazoline Hydrochloride Cream, 1%		RHOFADE Cream, 1%		Vehicle Cream
Arm/Group Description	Oxymetazoline hydrochloride cream, 1% Oxymetazoline Hydrochloride: Test Comparator		RHOFADE Cream, 1% Rhofade Cream, 1%: Reference Comparator		Vehicle cream Placebo: Placebo Comparator
All Cause Mortality
	Oxymetazoline Hydrochloride Cream, 1%		RHOFADE Cream, 1%		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/379 (0%)		0/382 (0%)		0/344 (0%)
Serious Adverse Events
	Oxymetazoline Hydrochloride Cream, 1%		RHOFADE Cream, 1%		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/379 (0%)		1/382 (0.3%)		1/344 (0.3%)
Cardiac disorders
Acute myocardial infarction	0/379 (0%)	0	1/382 (0.3%)	1	0/344 (0%)	0
Injury, poisoning and procedural complications
Clavicle fracture	0/379 (0%)	0	0/382 (0%)	0	1/344 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Oxymetazoline Hydrochloride Cream, 1%		RHOFADE Cream, 1%		Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/379 (16.1%)		60/382 (15.7%)		48/344 (14%)
Cardiac disorders
Acute myocardial infarction	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Endocrine disorders
Androgen deficiency	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Eye disorders
Eye irritation	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Crohn's disease	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Diarrhoea	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Dyspepsia	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Gastrooesophageal reflux disease	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
General disorders
Application site acne	4/379 (1.1%)		6/382 (1.6%)		2/344 (0.6%)
Application site dermatitis	3/379 (0.8%)		2/382 (0.5%)		1/344 (0.3%)
Application site dryness	5/379 (1.3%)		2/382 (0.5%)		1/344 (0.3%)
Application site erythema	7/379 (1.8%)		10/382 (2.6%)		7/344 (2%)
Application site exfoliation	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Application site hypoaesthesia	1/379 (0.3%)		1/382 (0.3%)		0/344 (0%)
Application site irritation	2/379 (0.5%)		0/382 (0%)		0/344 (0%)
Application site pain	9/379 (2.4%)		16/382 (4.2%)		10/344 (2.9%)
Application site papules	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Application site paraesthesis	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Application site pruritus	14/379 (3.7%)		16/382 (4.2%)		7/344 (2%)
Application site rash	2/379 (0.5%)		0/382 (0%)		0/344 (0%)
Application site reaction	8/379 (2.1%)		2/382 (0.5%)		1/344 (0.3%)
Application site swelling	1/379 (0.3%)		0/382 (0%)		1/344 (0.3%)
Oedema peripheral	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Pain	1/379 (0.3%)		1/382 (0.3%)		0/344 (0%)
Pyrexia	1/379 (0.3%)		1/382 (0.3%)		0/344 (0%)
Immune system disorders
Seasonal allergy	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Infections and infestations
Application site pustules	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Bronchitis	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Eyelid infection	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Influenza	1/379 (0.3%)		0/382 (0%)		2/344 (0.6%)
Nasopharyngitis	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Postoperative wound infection	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Tooth infection	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Upper respiratory tract infection	0/379 (0%)		0/382 (0%)		3/344 (0.9%)
Urinary tract infection	0/379 (0%)		0/382 (0%)		2/344 (0.6%)
Injury, poisoning and procedural complications
Arthropod bite	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Clavicle fracture	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Exposure to toxic agent	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Fall	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Head injury	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Muscle strain	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Sunburn	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Tooth fracture	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/379 (0%)		0/382 (0%)		2/344 (0.6%)
Arthritis	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Back pain	1/379 (0.3%)		1/382 (0.3%)		1/344 (0.3%)
Muscle spasms	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Musculoskeletal pain	2/379 (0.5%)		1/382 (0.3%)		0/344 (0%)
Myalgia	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Pain in jaw	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Nervous system disorders
Burning sensation	1/379 (0.3%)		1/382 (0.3%)		0/344 (0%)
Facial paralysis	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Headache	9/379 (2.4%)		11/382 (2.9%)		12/344 (3.5%)
Migraine	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Sinus headache	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Psychiatric disorders
Insomnia	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Reproductive system and breast disorders
Dysmenorrhoea	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/379 (0.3%)		1/382 (0.3%)		0/344 (0%)
Nasal congestion	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Rhinorrhoea	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Sinus congestion	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Skin and subcutaneous tissue disorders
Acne	3/379 (0.8%)		0/382 (0%)		0/344 (0%)
Erythema	2/379 (0.5%)		0/382 (0%)		1/344 (0.3%)
Ingrowing nail	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Pain of skin	1/379 (0.3%)		0/382 (0%)		0/344 (0%)
Papule	0/379 (0%)		1/382 (0.3%)		0/344 (0%)
Pruritus	1/379 (0.3%)		3/382 (0.8%)		0/344 (0%)
Rash	0/379 (0%)		0/382 (0%)		1/344 (0.3%)
Rash erythematous	1/379 (0.3%)		0/382 (0%)		0/344 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed.