Bioequivalence Study of Tretinoin Gel 0.05% to Brand Tretinoin Gel

• Sponsor: Spear Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02249767
• Collaborator: (none)
• Enrollment: 574
• Arms: 3
• Duration (Months): 7

Study Details

Study Description

Brief Summary

This was a double-blind, randomized, three-treatment, parallel study. Normal, healthy male and female children and adults (i.e., ages 12 to 40 years) with at least Grade 2 (i.e., mild severity) acne vulgaris were treated on the full face once daily for 84 days with the Tretinoin Gel 0.05%, Brand (tretinoin) Gel 0.05%, or Gel Vehicle. Acne lesions were graded by a single blinded observer at screening and at Weeks 0 (i.e., baseline), 2, 4, 8, and 12 at each location.

Condition or Disease	Intervention/Treatment	Phase
Acne	Drug: Tretinoin	Phase 3

Detailed Description

This was a double-blind, randomized, three-treatment, parallel study conducted at three locations with a single investigator. Normal, healthy male and female children and adults (i.e., ages 12 to 40 years) with at least Grade 2 (i.e., mild severity) acne vulgaris were treated on the full face once daily for 84 days with the Tretinoin Gel 0.05%, Brand (tretinoin) Gel 0.05%, or Gel Vehicle. Acne lesions were graded by a single blinded observer at screening and at Weeks 0 (i.e., baseline), 2, 4, 8, and 12 at each location.

The assigned study treatment was self-applied topically once daily for 84 consecutive days.

Scheduled study visits included:

• Visit 1 (Baseline Visit, Day 0)

• Visit 2 (First Interim Visit, Day 14)

• Visit 3 (Second Interim Visit, Day 28)

• Visit 4 (Third Interim Visit, Day 56)

• Visit 5 (Forth Interim Visit, Day 84)

A window of ± 4 days was considered acceptable for each scheduled visit following the Baseline Visit. Subjects were admitted into the study if they had a clinical diagnosis of acne vulgaris and if they met the inclusion/exclusion criteria. During the study visits, the following procedures were performed:

• Counts of inflammatory, non-inflammatory, and nodulocystic lesions

• The Investigator's Global Assessment (IGA)

• Assessment of application site reactions Safety was assessed by the monitoring of AEs and documenting signs and/or symptoms of application site reactions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 574 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Bioequivalence Study of Tretinoin Gel 0.05% to Brand Tretinoin Gel
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Generic Tretinoin Treatment of acne once daily over 12 weeks	Drug: Tretinoin; Treatment of acne once daily in evening; Other Names: Placebo
Active Comparator: Brand Tretinoin Treatment of Acne once daily over 12 weeks	Drug: Tretinoin; Treatment of acne once daily in evening; Other Names: Placebo
Placebo Comparator: Placebo Vehicle Treatment of acne once daily over 12 weeks	Drug: Tretinoin; Treatment of acne once daily in evening; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change in Baseline Acne Lesions at Week 12 [Baseline and 12 weeks]

   Percent change in baseline in inflammatory and non-inflammatory lesions at week 12.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Normal, healthy male and female children and adults aged 12 to 40 years

• Written and verbal informed consent had to be obtained. Subjects aged 12 to 17 years, had to sign an assent for the study and a parent or a legal guardian had to sign the informed consent

• Women of childbearing potential had to be non-pregnant and non-nursing, and had to be willing to avoid pregnancy during the course of the study and during the menstrual cycle following completion of their participation in the study. Adequate contraception was defined as systemic birth control, such as oral contraceptives, for three months prior and implantable/injectable contraceptives (e.g., Norplant, intrauterine device [IUD]) for six months prior to study drug administration; or barrier methods, such as diaphragm plus spermicide or condom plus spermicide, consistently for at least 14 days prior to study drug administration; or abstinence.

• On the face, having ≥ 20 inflammatory (i.e., papules and pustules) and ≥ 25 non-inflammatory (i.e., open and closed comedones) lesions with ≤ 2 nodulocystic lesions (i.e, nodules and cysts), as per FDA Draft Guidance on Tretinoin, dated March 20

• Able to refrain from the use of all other topical acne medications or antibiotics during the treatment period

• Considered reliable and capable of understanding their responsibility and role in the study

Exclusion Criteria:

• Presence of any skin condition that would interfere with the diagnosis or assessment of acne vulgaris (e.g., on the face: rosacea, dermatitis, psoriasis, squamous cell carcinoma, eczema, acneform eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis). Note: Eczema and psoriasis on the body are not exclusions.

• Subjects with active cystic acne as evidenced by more than 2 facial nodules. Nodules are defined as in 7.3.3 as: deep-seated in the skin (i.e., centered in the dermis or subcutis) and greater than 5 mm in diameter.

• More than 40 papules and/or pustules (inflammatory lesions).

• More than 60 open and/or closed comedones/milia (non-inflammatory lesions).

• Overall severity grade of less than 2 or greater than 4.

• History of allergy or hypersensitivity to tretinoin, retinoids, or any of the study medication ingredients.

• Significant history or clinical evidence of auto-immune, cardiovascular, gastrointestinal, hematological, hepatic, neurological, pancreatic, or renal disease.

• Use within 6 months prior to baseline of systemic retinoid (isotretinoin) treatment or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).

• Oral contraceptives started or changed within 3 months prior to study initiation or planned to change during the study.

• Use on the face within 1 month prior to baseline of 1) cryodestruction or chemodestruction, 2) dermabrasion, 3) photodynamic therapy, 4) acne surgery, 5) intralesional steroids, or 6) x-ray therapy.

• Use within 1 month prior to baseline of 1) spironolactone, 2) systemic steroids, 3) systemic antibiotics, 4) systemic treatment for acne vulgaris (other than oral retinoids, which require a 6-month washout), or 5) systemic anti-inflammatory agents.

• Use within 2 weeks prior to baseline of 1) topical steroids, 2) topical retinoids, 3) topical acne treatments including over-the-counter preparations, 4) topical anti-inflammatory agents, or 5) topical antibiotics.

• Pregnant or breast-feeding.

• Serious psychological illness.

• Significant history (within the past year) of alcohol or drug abuse.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Spear Pharmaceuticals

Investigators

• Principal Investigator: Susan Barker, MD, Moore Clinical Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spear Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02249767
• Other Study ID Numbers: Tret.2014.10.01.14
• First Posted: Sep 26, 2014
• Last Update Posted: Feb 10, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Tretinoin

Study Results

Participant Flow

Arm/Group Title	Generic Tretinoin	Brand Tretinoin	Placebo Vehicle
Arm/Group Description	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Treatment of Acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening
Period Title: Overall Study
STARTED	230	229	115
COMPLETED	222	220	107
NOT COMPLETED	8	9	8

Baseline Characteristics

Arm/Group Title	Generic Tretinoin	Brand Tretinoin	Placebo Vehicle	Total
Arm/Group Description	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Treatment of Acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Total of all reporting groups
Overall Participants	222	220	107	549
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	20.1 (7.06)	20.1 (7.60)	19.6 (7.31)	20.0 (7.32)
Sex: Female, Male (Count of Participants)
Female	124 55.9%	131 59.5%	64 59.8%	319 58.1%
Male	98 44.1%	89 40.5%	43 40.2%	230 41.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	0 0%	0 0%	1 0.2%
Asian	1 0.5%	3 1.4%	2 1.9%	6 1.1%
Native Hawaiian or Other Pacific Islander	2 0.9%	1 0.5%	1 0.9%	4 0.7%
Black or African American	57 25.7%	46 20.9%	24 22.4%	127 23.1%
White	111 50%	109 49.5%	61 57%	281 51.2%
More than one race	50 22.5%	60 27.3%	16 15%	126 23%
Unknown or Not Reported	0 0%	1 0.5%	3 2.8%	4 0.7%
Region of Enrollment (participants) [Number]
United States	222 100%	220 100%	107 100%	549 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Baseline Acne Lesions at Week 12
Description	Percent change in baseline in inflammatory and non-inflammatory lesions at week 12.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

This is Per protocol population (PP) Analysis. Generic Tretinoin Intent to Treat (ITT) started 222- 22 excluded as not following protocol= 200 PP. Brand Tretinoin 220 ITT - 11 excluded not following Protocol=209 PP. Placebo 107 ITT - 7 excluded = 100 PP Percent change from baseline in acne lesions

Arm/Group Title	Generic Tretinoin	Brand Tretinoin	Placebo Vehicle
Arm/Group Description	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Treatment of Acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening
Measure Participants	200	209	100
Mean (Standard Deviation) [Percent reduction]	-32.34 (30.35)	-37.32 (28.81)	-26.38 (32.33)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Treatment related irritation
Arm/Group Title	Generic Tretinoin		Brand Tretinoin		Placebo Vehicle
Arm/Group Description	Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening		Treatment of Acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening		Treatment of acne once daily over 12 weeks Tretinoin: Treatment of acne once daily in evening
All Cause Mortality
	Generic Tretinoin		Brand Tretinoin		Placebo Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/230 (0%)		0/229 (0%)		0/115 (0%)
Serious Adverse Events
	Generic Tretinoin		Brand Tretinoin		Placebo Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/230 (0%)		0/229 (0%)		0/115 (0%)
Other (Not Including Serious) Adverse Events
	Generic Tretinoin		Brand Tretinoin		Placebo Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/230 (21.3%)		46/229 (20.1%)		26/115 (22.6%)
Skin and subcutaneous tissue disorders
Irritation from Drug	49/230 (21.3%)		46/229 (20.1%)		26/115 (22.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

With OK from Sponsor