Clinical trial NCT03717506
Conditions: Acne Vulgaris
Keywords: zits pimples blackheads
Sponsor: Balmoral Medical company
Start date: 2018-10-10; Completion date: 2020-04-16
Enrollment: 1236 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The objective of the study is to evaluate the safety, tolerability, and therapeutic equivalence of GDC 268 to Clindamycin Phosphate Topical Lotion, 1% and to compare the efficacy of these two products to the GDC vehicle lotion (i.e., placebo) in the treatment of acne vulgaris.

Detailed description:

Arms: arm 1: GDC 268 Lotion applied topically as directed. arm 2: Clindamycin Phosphate Lotion, 1% applied topically as directed. arm 3: GDC Vehicle lotion applied topically as directed.
Interventions: intervention 1: GDC 268 Lotion intervention 2: Clindamycin Phosphate Lotion 1% intervention 3: GDC Vehicle Lotion
Intervention descriptions: intervention 1: GDC 268 is a topical lotion intervention 2: Clindamycin Phosphate Lotion is an FDA-approved drug product intervention 3: GDC Vehicle Lotion contains 0.0% of active drug and is matched to the other two active test drugs

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Page 1 of 66 
 
CONTROLLED & CONFIDENTIAL 
 
A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, PARALLEL GROUP COMPARISON STUDY TO DETERMINE 
THE THERAPEUTIC EQUIVALENCE OF GDC 268 AND CLINDAMYCIN 
PHOSPHATE TOPICAL LOTION, 1% IN SUBJECTS WITH ACNE VULGARIS 
 
PROTOCOL NUMBER: 
GDC-268-001 
TI PROJECT NUMBER: 
209-1251-301 
ORIGINAL PROTOCOL:  
May 24, 2018 
PROTOCOL VERSION: 
3.0 
AMENDMENT #1: 
January 15, 2019 
AMENDMENT #2: 
September 6, 2019 
FILENAME: 
GDC-268-001_pro_06Sep2019_v3.0.docx 
SPONSOR: 
Gage Development Company, LLC 
9450 W Bryn Mawr Ave., Ste. 640 
Rosemont, IL 60018 
SPONSOR REPRESENTATIVE: 
 
 
Gage Development Company, LLC 
MEDICAL MONITOR: 
 
Therapeutics, Inc. 
9025 Balboa Avenue, Suite 100 
San Diego, CA 92123 
 
 
 
 
PROJECT MANAGER: 
 
Therapeutics, Inc. 
9025 Balboa Avenue, Suite 100 
San Diego, CA 92123 
 
 
 
 
24 Hour Emergency Telephone Number 
619-889-7058 
 
Therapeutics, Incorporated 
9025 Balboa Avenue, Suite 100, San Diego, CA 92123 
 
The information contained in this document is confidential and proprietary property of 
Gage Development Company, LLC. 




Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 3 of 66 
 
CONTROLLED & CONFIDENTIAL 
STUDY ACKNOWLEDGEMENT 
I understand this protocol contains information that is confidential and proprietary to 
Gage Development Company, LLC, the Sponsor. 
 
I have read this protocol, agree that it contains all the details necessary to conduct the 
study as described, and will conduct this study following this protocol. 
 
I will provide the contents of this protocol to study staff under my direct supervision that 
need to know the contents to conduct the study. I will discuss this information with the 
study staff to ensure they are fully informed about the study and the test articles. I will 
provide the contents of the protocol to the responsible Institutional Review Board(s). 
These disclosures may be made; providing the contents are not used in any other clinical 
study and they are not disclosed to any other person or entity without prior written 
consent from Gage Development Company, LLC. This condition does not apply to 
disclosure required by government regulations or laws; however, I agree to give prompt 
notice to Gage Development Company, LLC of any such disclosure. 
 
I understand the study may be terminated or enrollment suspended at any time by Gage 
Development Company, LLC, with or without cause, or by me if it becomes necessary 
to protect the interests of the study subjects. 
 
Any additional information added to this protocol is also confidential and proprietary to 
Gage Development Company, LLC and must be treated in the same manner as the 
contents of this protocol. 
 
____________________________________ 
Printed Name of Principal Investigator 
 
____________________________________ 
 
_____________________ 
Investigator Signature  
 
 
 
 
Date 
 
Protocol number: GDC-268-001 
 
 
 
Site number:              
 
 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 4 of 66 
 
CONTROLLED & CONFIDENTIAL 
PROTOCOL SYNOPSIS 
Title 
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel 
Group Comparison Study to Determine the Therapeutic Equivalence of 
GDC 268 and Clindamycin Phosphate Topical Lotion, 1% in Subjects with 
Acne Vulgaris 
Study Type 
Bioequivalence with Clinical Endpoint 
Test Articles 
1. Test product: GDC 268 (Gage Development Company, LLC) 
2. Reference Product: Clindamycin Phosphate Topical Lotion, 1% 
(GREENSTONE® BRAND) 
3. Placebo: GDC Vehicle (Gage Development Company, LLC) 
Study Objective 
To evaluate the safety, tolerability, and therapeutic equivalence of GDC 268 
to Clindamycin Phosphate Topical Lotion, 1% and to compare the efficacy 
of these two products to the GDC vehicle lotion (i.e., placebo) in the 
treatment of acne vulgaris. 
Study Design 
Multicenter, randomized, double-blind, placebo-controlled, parallel group 
comparison. 
Treatment Groups 
Eligible subjects will be randomized (2:2:1) to treatment with GDC 268, 
Clindamycin Phosphate Topical Lotion, or GDC Vehicle. 
Duration of Treatment 
Twice daily for 12 weeks. 
Duration of Study 
Each subject will participate for approximately 12 weeks, in addition to the 
screening visit. 
Study Population 
Healthy male or female subjects 12 to 40 years of age (inclusive) with a 
clinical diagnosis of mild to severe facial acne vulgaris (Grade 2, 3, or 4 on 
the Investigator’s Global Assessment [IGA]), 25-100 non-inflammatory 
lesions (i.e., open and closed comedones), 20-70 inflammatory lesions (i.e., 
papules and pustules), and ≤2 nodulocystic lesions ( nodules and cysts) on 
the face. 
Total Number of 
Subjects 
Approximately 1200 subjects will be enrolled to obtain at least 1153 
modified intent-to-treat (mITT) and at least 865 per-protocol (PP) subjects 
in the study. 
Number of Sites 
Approximately 50 sites will participate in the study. 
Inclusion Criteria 
To enter the study, a subject must meet the following criteria:  
 
1. 
Subject is a healthy male or non-pregnant, non-breastfeeding female 
12 to 40 years of age (inclusive) at the time of consent/assent.  
2. 
Subject has provided written informed consent/assent. A subject 
under 18 years of age must provide written informed assent and be 
accompanied by the parent or legal guardian at the time of 
assent/consent signing. The parent or legal guardian must provide 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 5 of 66 
 
CONTROLLED & CONFIDENTIAL 
informed consent for the subject. If a subject becomes 18 years of age 
during the study, the subject must provide written informed consent 
at that time to continue study participation. 
3. 
Subject has a clinical diagnosis of mild to severe facial acne vulgaris 
defined as Grade 2, 3, or 4 on the IGA at Baseline. 
4. 
Subject must have ≥ 25 but ≤ 100 non-inflammatory lesions (open 
and closed comedones) AND ≥ 20 but ≤ 70 inflammatory lesions 
(papules and pustules) AND ≤ 2 nodulocystic lesions (nodules and 
cysts) on the face (e.g., forehead, nose, cheeks, chin, upper lip) at 
Baseline. 
5. 
Subject and parent/guardian (if applicable) are willing and able to 
apply the test article(s) as directed, comply with study instructions, 
and commit to all follow-up visits for the duration of the study. 
6. 
Subject must be willing and able to refrain from use of all other 
topical products in the Treatment Area, all acne medications other 
than test article, and all antibiotics (other than test article) during the 
12-week treatment period. 
7. 
Subject, in the investigator’s opinion, is in good general health and 
free of any disease state or physical condition that might impair 
evaluation of facial acne vulgaris or otherwise impact the integrity of 
the study, or exposes the subject to an unacceptable risk by study 
participation.  
8. 
Females must be surgically sterile1 or use an effective method of birth 
control.2,3 Women of childbearing potential (WOCBP) must have a 
negative urine pregnancy test (UPT)4 at Baseline.  
9. 
Subject has used the same type and brand of make-up, cleanser or 
other non-medicated facial products and hair products (e.g., Clinique 
foundation, Cetaphil soap, shampoo, hair gel, hairspray, mousse, etc.) 
for at least 4 weeks prior to Visit 1/Baseline and agrees to continue 
and not change his/her other general skin care and hair care products 
and regimen for the entire study. NOTE: Subjects who change from 
using a medicated acne cleanser that contains benzoyl peroxide, 
salicylic acid, etc. to using a bland non-medicated/non-acne cleanser 
                                                 
 
1 Hysterectomy, bilateral tubal ligation (at least 6 months prior to initiation of treatment), or bilateral 
oophorectomy. 
2 Effective forms of birth control include a) hormonal contraceptives [e.g., oral, transdermal, injectable, 
implantable, or vaginal ring] (see next footnote), b) intrauterine device (IUD), c) barrier methods [condom 
and spermicidal or diaphragm/cervical cap and spermicidal], d) monogamous relationship with a partner who 
is sterile [e.g., vasectomy performed at least 6 months prior to study entry], or e) total abstinence for subjects 
who are not sexually active. Subjects who become sexually active or begin to have relations with a partner 
of the opposite sex who is not sterile during the study must agree to use an effective form of birth control for 
the duration of the study.  
3 WOCBP taking hormonal therapy (e.g., oral, transdermal, injectable, implantable, vaginal ring) must be on 
treatment prior to study entry, continued per label, and must not change their dosing regimen during the 
study. WOCBP taking hormonal therapy for any reason must be on the same treatment for at least 3 
months prior to study entry. Those who have used hormonal therapy prior to study entry must have 
discontinued use at least 8 weeks prior to the start of the study. NOTE: Subjects using hormonal therapy for 
acne management should not be allowed to enroll unless they have washed out of this therapy for at least 8 
weeks prior to study entry. 
4 UPT must have a minimum sensitivity of 25 mIU ß-hCG/mL. 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 6 of 66 
 
CONTROLLED & CONFIDENTIAL 
prior to Visit 1/Baseline will only be required to have used the new 
non-acne cleanser for at least 2 weeks in order to establish a stable 
skin care regimen. 
Exclusion Criteria 
A subject is ineligible to enter the study if he/she meets one or more of the 
following criteria: 
 
1. 
Subject is pregnant, breastfeeding, or is planning to become pregnant 
or breastfeed during the study. 
2. 
Subject has active nodulocystic acne or acne conglobata, acne 
fulminans, or other forms of acne (e.g., acne mechanica). 
3. 
Subject has more than 2 facial nodules/cysts (where nodule/cyst is 
defined as an inflammatory lesion greater than or equal to 0.5 cm in 
size with or without cystic changes). 
4. 
Subject has any skin condition that, in the investigator’s opinion, 
could 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).  
5. 
Subject has excessive facial hair (e.g., beards, sideburns, 
moustaches), facial tattoos, or other facial attributes that would 
interfere with diagnosis or assessment of acne vulgaris in the opinion 
of the investigator. 
6. 
Subject has a history of hypersensitivity or allergy to clindamycin or 
lincomycin and/or any of the ingredients in the test articles. 
7. 
Subject has a history of regional enteritis or ulcerative colitis, or a 
history of antibiotic-associated colitis. 
8. 
Subject is atopic (e.g., atopic dermatitis, allergic rhinitis, allergic 
asthma). Note: Subjects that are not atopic but have a component(s) 
of this syndrome may be enrolled (e.g., a person with allergic rhinitis 
or allergic asthma).  
9. 
Subject has used any of the following topical preparations or 
procedures on the face: 
 
Topical retinoids (e.g., tazarotene, adapalene, and tretinoin) 
within 2 weeks prior to Baseline; 
 
Topical anti-acne treatments including, but not limited to, over-
the-counter (OTC) acne cleansers, soaps, washes or treatments, 
benzoyl peroxide, antibiotics, azelaic acid, dapsone, sulfa based 
products, corticosteroids, and salicylic acid within 2 weeks prior 
to Baseline; 
 
Topical steroids within 2 weeks prior to Baseline. 
 
Topical antibiotics within 2 weeks prior to Baseline. 
 
Topical anti-inflammatory agents within 2 weeks prior to 
Baseline; 
 
Cryodestruction 
or 
chemodestruction, 
dermabrasion, 
photodynamic therapy including other light-based and laser 
therapies, acne surgery, intralesional steroids, or x-ray therapy 
within 4 weeks prior to Baseline; 
 
Other topical therapy, which may materially affect the subject’s 
acne, in the investigator’s opinion. 
10. 
Subject has used any of the following systemic medications: 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 7 of 66 
 
CONTROLLED & CONFIDENTIAL 
 
Corticosteroids (including intramuscular, intra-articular, and 
intralesional injections) for any indication within 4 weeks prior 
to Baseline; 
 
Antibiotics5 for any indication or other systemic anti-acne 
medications within 4 weeks prior to Baseline; 
 
Androgen receptor blockers (e.g., spironolactone, flutamide) 
within 4 weeks prior to Baseline; 
 
Retinoid therapy (e.g., isotretinoin) within 6 months prior to 
Baseline; 
 
Vitamin A supplements (greater than 10,000 units per day) 
within 6 months prior to Baseline; 
 
Anti-inflammatory agents or immunosuppressive drugs within 4 
weeks prior to Baseline; 
 
Neuromuscular blocking agents such as botulinum toxin type A 
(e.g., BOTOX, DYSPORT) within 2 weeks prior to Baseline; 
 
Other systemic therapy, which may materially affect the 
subject’s acne, in the investigator’s opinion. 
11. 
Subject has used oral contraceptives or estrogen for less than 3 
months prior to Baseline. 
12. 
Subject is planning surgery during the study. 
13. 
Subject has the need or plans to be exposed to artificial tanning 
devices or excessive sunlight during the study. 
14. 
Subject is currently enrolled in an investigational drug, device, or 
biologic study. 
15. 
Subject has used an investigational drug or investigational device 
treatment within 30 days prior to first application of the test article. 
16. 
Subject is known to be noncompliant or is unlikely to comply with 
the requirements of the study protocol (e.g., due to alcoholism, drug 
dependency, mental incapacity) in the opinion of the investigator.  
17. 
Subject and parent/guardian (if applicable) are unable to 
communicate or cooperate with the investigator due to language 
problems, poor mental development, or impaired cerebral function. 
Study Procedures 
Subjects can be screened for the study up to 45 days before Baseline. During 
screening, the study requirements will be reviewed, written informed 
consent/assent obtained, and eligibility confirmed. These procedures may be 
combined with the Baseline Visit if wash out from prohibited medications is 
not required. If applicable, qualified subjects can wash out from prohibited 
acne medications or treatments prior to their Baseline Visit once they have 
been consented. Subjects who require washout for longer than 45 days will 
be re-consented.  
 
The study will consist of a Screening/Baseline Visit, a follow-up telephone 
call at Week 2, and follow-up visits at Weeks 4, 8, and 12. An unscheduled 
in-office follow-up visit may be done at the discretion of the investigator for 
subjects with tolerability issues or a material adverse event (AE) concern. 
 
                                                 
 
5 Contact the Medical Monitor if a subject requires concomitant antibiotic therapy. 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 8 of 66 
 
CONTROLLED & CONFIDENTIAL 
Visit 1 (Day 1): Screening/Baseline. The following will be obtained at this 
visit: signed written informed consent/assent (or re-consent/assent if 
washout period exceeds 45 days), confirmation of eligibility, medical 
history, 
demographics, 
review 
of 
concomitant 
medications 
and 
procedures/therapies, dermatologic exam, vital signs (with height and 
weight), a UPT for WOCBP, clinical evaluations (IGA and lesion counts), 
local skin reaction (LSR) assessment, and standardized photography of the 
face. Qualified subjects will be randomly assigned to one of three treatment 
groups (GDC 268, Reference Product, or GDC Vehicle). Randomization will 
be blocked from a centralized schedule and stratified by the number of non-
inflammatory lesions (≤70 / > 70) present at the Baseline visit. Subject kits 
will be dispensed according to the kit number assigned by an Interactive Web 
Response System (IWRS) as subjects are enrolled. Test article application 
will be demonstrated using the non-medicated samples provided to the site 
and, as part of training, the subject will apply the non-medicated sample in 
the clinic under staff supervision to ensure proper application. The subject 
will be instructed not to open study supplies at the site. Test article will be 
dispensed along with application instructions, and a Subject Diary will be 
provided to document applied or missed doses. Subjects will be instructed to 
apply the test article twice daily, once in the morning and once in the 
evening, for 12 weeks with the first dose to be applied on the evening of the 
Baseline Visit. The subject will be scheduled for a follow-up telephone call. 
 
Visit 2 (Week 2): Follow-Up Telephone Call. The site staff will contact the 
subject to confirm the next visit appointment, review the Subject Diary and 
test article compliance, review of concomitant medications and 
procedures/therapies, and query the subject about AEs. The site staff will 
remind the subject to continue to apply test article twice daily, once in the 
morning and once in the evening and to bring all bottles (used and unused) 
of test article with him/her to the next clinic visit and to not apply test article 
or other products to the face within 4 hours of the next clinic visit. Subjects 
with tolerability issues or a material AE concern of any type may be seen for 
an in-office follow-up as an unscheduled visit at the discretion of the 
investigator. 
 
Visits 3 and 4 (Weeks 4 and 8): Follow-Up. The subject will return to the 
clinic for review of concomitant medications and procedures/therapies, 
LSRs, and AEs. Clinical evaluations (IGA and lesion counts) will be 
performed. The Subject Diary will be reviewed/collected/distributed as 
necessary and test article compliance will be reviewed; the site staff will 
remind the subject to continue to apply test article twice daily, once in the 
morning and once in the evening, until the next clinic visit and to not apply 
test article or other products to the face within 4 hours of the next clinic visit. 
Test article application will be demonstrated if deemed necessary. Test 
article accountability will be documented. The subject will be scheduled for 
the next visit. 
 
Visit 5 (Week 12): End of Study (EOS) or Early Termination (ET). The 
subject will return to the clinic for review of concomitant medications and 
procedures/therapies, LSRs, and AEs. A UPT for WOCBP and clinical 
evaluations (IGA and lesion counts) will be performed. The Subject Diary 
will be reviewed and test article compliance will be reviewed. Test article 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 9 of 66 
 
CONTROLLED & CONFIDENTIAL 
accountability will be documented; all test articles and subject diaries will 
be collected. The subject will exit the study. 
 
Unscheduled Visit. The investigator may see the subject at an unscheduled 
visit to manage any AEs or LSRs (if applicable). The subject will return to 
the clinic for review of concomitant medications and procedures/therapies, 
LSRs, and AEs. The Subject Diary and test article compliance will be 
reviewed. The subject’s next appointment will be confirmed. 
Study Measurements 
Dosing Compliance: 
Measures of test article compliance will include the duration (days) of 
treatment (defined as last dose date – first dose date +1), the total number of 
applications applied and missed (determined from the doses reported in the 
Subject Diary), and the percent of expected doses applied. A subject will be 
considered compliant with the dosing regimen if the subject applies at least 
75% and no more than 125% of the expected test article applications for the 
specified duration of the study and does not miss the scheduled applications 
for more than 3 consecutive days. 
 
Efficacy and safety measurements will be assessed according to the schedule 
of events. 
 
Efficacy: 
Investigator’s Global Assessment 
Overall severity of acne will be assessed using a five-point scale where 
0=Clear, 1=Almost Clear, 2=Mild, 3=Moderate, and 4=Severe. This is a 
static morphological scale that refers to a point in time and not a comparison 
to Baseline. 
 
Acne Lesion Counts 
The number of non-inflammatory lesions (open and closed comedones) and 
inflammatory lesions (papules and pustules) on the face (including those 
present on the nose) will be counted. Counts of nodules and cysts will be 
reported separately and are not to be included in the inflammatory or non-
inflammatory lesion counts. 
 
Safety: 
Adverse Events 
All reported or observed AEs will be recorded. At each visit, subjects will 
also be questioned specifically about the status of any ongoing AEs. 
Untoward events that occur prior to the first dose of test article will be 
captured in the Medical History section of the electronic case report form 
(eCRF) unless they are related to a study-specific procedure. 
 
Local Skin Reactions 
At each visit, LSRs (erythema, edema, scaling/dryness, stinging/burning, 
pruritus, erosion, and pain) will be assessed. Erythema, edema, 
scaling/dryness, and erosion will be assessed by the investigator and 
stinging/burning, pain, and pruritus will be assessed by the subject. 
Assessments will be made using a 4-point ordinal scale where 0=absent, 
1=mild (slight, barely perceptible), 2=moderate (distinct presence), and 
3=severe (marked, intense). Only LSRs that require medical intervention 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 10 of 66 
 
CONTROLLED & CONFIDENTIAL 
(e.g., prescription medication), require withholding or discontinuation of the 
application of the test article, or extend 2 cm beyond the Treatment Area will 
be documented as AEs. Any LSRs that are not listed above will be recorded 
as an AE. 
 
Vital Signs 
Vital signs including temperature, systolic and diastolic blood pressure, heart 
rate, and respiration rate will be measured at Visit 1/Baseline. Assessments 
will be made after the subject has rested in a seated position for at least 5 
minutes. Height and weight will also be measured at Visit 1/Baseline. 
 
Urine Pregnancy Tests 
A UPT will be performed at Visit 1/Baseline and at Visit 5/Week 12/EOS 
for WOCBP. 
Study Endpoints 
Co-Primary Efficacy Endpoints: 
 
Percent change from Baseline to Week 12 in the inflammatory 
(papules and pustules) lesion count. 
 
Percent change from Baseline to Week 12 in the non-inflammatory 
(open and closed comedones) lesion count. 
 
Safety Endpoints: 
 
Incidence (severity and causality) of any reported or observed 
treatment emergent AEs, whether or not they are considered to be 
related to the test article.  
 
Number of subjects with improved/same versus worsened 
severities compared to Baseline of the following LSRs: erythema, 
edema, scaling/dryness, stinging/burning, pruritus, erosion, and 
pain at each onsite treatment visit. 
Sample Size 
Calculations 
Based on the assumption of a 40% reduction in inflammatory and non-
inflammatory lesions counts for the Reference Product and a 38% reduction 
for GDC 268, 346 PP subjects per active arm will provide 85% probability 
of demonstrating therapeutic equivalence between the two active treatments 
at an alpha=0.05 (two one-sided tests) with 90% confidence interval bounds 
of the ratio of means being 0.08 and 1.25. Assuming a 25% reduction in 
inflammatory and non-inflammatory lesions counts for the VEH, 231 mITT 
subjects in the VEH arm and 462 mITT subjects in each of the active 
treatment arms will provide at least an 85% probability of demonstrating that 
each active treatment is statistically superior to vehicle treatment at a two-
sided alpha of 0.05. Therefore, approximately 1200 subjects will be enrolled 
using a 2:2:1 randomization ratio (GDC 268:Reference Product:VEH) to 
obtain a total of 1155 mITT subjects and 865 PP subjects. 
Statistical Methods 
All statistical processing will be performed using SAS® Version 9.4 unless 
otherwise stated.  
 
Study Populations: 
The Safety population will include all randomized subjects who applied at least 
one dose of test article.  
 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 11 of 66 
 
CONTROLLED & CONFIDENTIAL 
The mITT population will include all randomized subjects who applied at least 
one dose of test article. 
 
The PP population will include all mITT subjects who met all 
inclusion/exclusion criteria, were compliant with the assigned test articles 
based on the subject diaries (applied at least 75% and no more than 125% of 
the expected test article applications for the specified duration of the study), 
did not miss the scheduled test article applications for more than 3 consecutive 
days (i.e., 3 consecutive days with no test article application), have no other 
evidence of material dosing noncompliance, and completed the primary 
endpoint evaluation at Week 12 within the designated visit window (Day 85 ± 
4 days) with no protocol violations that would affect the treatment evaluation 
including use of the prohibited medications.  
 
Subject randomization will be stratified by the number of non-inflammatory 
lesions (≤70 / >70) present at the Baseline Visit in order to ensure balanced 
enrollment of subjects across the treatment groups by non-inflammatory 
lesion count. No subset analyses are planned based on baseline non-
inflammatory lesion counts. 
 
Dosing Compliance: 
Descriptive statistics will be used to summarize test article compliance for 
each analysis population. Compliant subjects are defined as those who apply 
at least 75% and no more than 125% of the expected test article applications, 
and did not miss scheduled applications for more than 3 consecutive days. 
The percentage of compliant subjects will be also presented. 
 
Efficacy Analyses: 
The efficacy analyses will be conducted on the mITT and PP populations. 
 
Primary Endpoints 
For each of the co-primary endpoints (percent change from Baseline at Week 
12 in the inflammatory lesion counts and in the non-inflammatory lesion 
counts), the 90% confidence interval of the ratio of the mean percent 
reduction in lesion counts between the GDC 268 group and the Reference 
Product group will be assessed in the PP population. If the 90% confidence 
intervals are contained within the interval [0.8, 1.25] for both inflammatory 
and non-inflammatory lesions, bioequivalence between GDC 268 and the 
Reference Product will be demonstrated. 
 
The percent change from Baseline at Week 12 in the inflammatory lesion 
counts and in the non-inflammatory lesion counts for each GDC 268 and 
Reference Product group will be compared against VEH group at an 
alpha=0.05 (p<0.05) in the mITT population using last observation carried 
forward (LOCF) imputation using analysis of variance (ANOVA) with 
factor of treatment in the statistical model using original percent change 
values.  
 
If the distribution of percent change from Baseline in the lesion counts are 
significantly skewed, the analyses will be performed based on rank 
transformed data. 
 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 12 of 66 
 
CONTROLLED & CONFIDENTIAL 
Exploratory Endpoint 
The frequency distribution of the observed and change from Baseline IGA 
scores will be presented at each visit by treatment group for the mITT and 
PP populations.  
 
Safety Analyses:  
All safety analyses will be performed in the Safety population unless 
otherwise stated. 
 
Adverse Events 
All AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) coding dictionary. The number and percent of unique 
subjects reporting each treatment-emergent AE will be summarized by 
MedDRA system organ class (SOC), MedDRA preferred term (PT), and 
treatment group. AEs will also be similarly summarized by SOC, PT, 
maximum severity, and treatment group as well as by SOC, PT, closest 
relationship to test article, and treatment group. All AEs reported during the 
study will be listed.  
 
Local Skin Reactions 
The frequency of the individual LSRs (erythema, edema, scaling/dryness, 
stinging/burning, pruritus, erosion, and pain) will be tabulated by severity 
and treatment group at each onsite clinic visit. Subject counts for 
improved/same versus worsened compared to Baseline value will be also 
presented for the post-baseline visits. 
 
 




Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 14 of 66 
 
CONTROLLED & CONFIDENTIAL 
1 An unscheduled in-office follow-up visit may be done at the discretion of the investigator for subjects with 
tolerability issues or a material AE concern. 
2 Consent/assent may be performed up to 45 days prior to Baseline. Subjects who require “washout” for 
longer than 45 days will be re-consented. 
3 Vital signs assessment will be performed after the subject has rested in a seated position for at least 5 
minutes and will include temperature, systolic and diastolic blood pressure, heart rate, and respiration rate. 
Height and weight will also be measured at Visit 1/Baseline. 
4 UPTs must have a minimum sensitivity of 25 mIU ß-hCG/mL. 
5 WOCBP include any female who has experienced menarche or is 10 years of age or older and who has not 
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy). 
6 Study staff will provide a Subject Instruction Sheet to the subject and parent/guardian (if applicable) and 
test article application will be demonstrated using the non-medicated samples provided to the site.  
7 Review Subject Diary and amount of test article used since last visit to determine subject compliance. Re-
educate subject on use of the test article with particular attention to inappropriate prior use of test article – 
be it amount of product applied and/or frequency of use. 
 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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ABBREVIATIONS 
AE 
Adverse Event 
ANOVA 
Analysis of Variance 
AV 
Acne Vulgaris 
β-hCG 
Beta-Human Chorionic Gonadotropin 
C. difficile 
Clostridium difficile 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EMR 
Electronic Medical Record 
EOS 
End of Study 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GDC 268 
Clindamycin phosphate topical lotion, 1% (Gage Development 
Company) 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator Brochure 
I/E 
Inclusion/Exclusion 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
IWRS 
Interactive Web Response System 
LOCF 
Last Observation Carried Forward 
LSR 
Local Skin Reaction 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
mIU 
Milli International Units 
mL 
Milliliter 
NSAID 
Nonsteroidal Anti-inflammatory Drug 
OTC 
Over-the-Counter 
PP 
Per-Protocol 
PT 
Preferred Term 
rRNA 
Ribosomal Ribonucleic Acid 
SAE 
Serious Adverse Event 
SE 
Self-Emulsifying 
SOC 
System Organ Class 
TI 
Therapeutics, Inc. 
UPT 
Urine Pregnancy Test 
VEH 
Vehicle 
WHO 
World Health Organization 
WOCBP 
Women of Childbearing Potential 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
TABLE OF CONTENTS 
Protocol Approval ............................................................................................................... 2 
Study Acknowledgement .................................................................................................... 3 
Protocol Synopsis................................................................................................................ 4 
Schedule of Events ............................................................................................................ 13 
Abbreviations  ................................................................................................................... 15 
Table of Contents .............................................................................................................. 16 
1. 
Background ....................................................................................................... 19 
2. 
Rationale ........................................................................................................... 19 
3. 
Objective ........................................................................................................... 20 
4. 
Study Design ..................................................................................................... 20 
5. 
Study Population ............................................................................................... 21 
5.1 
Subject Eligibility ............................................................................................. 21 
5.1.1 
Inclusion Criteria ....................................................................................... 21 
5.1.2 
Exclusion Criteria ...................................................................................... 22 
5.1.3 
Subject Withdrawal Criteria ...................................................................... 24 
5.1.4 
Enrollment of Protected Population .......................................................... 24 
5.1.5 
Subjects from the Same Household ........................................................... 25 
6. 
Test Articles and Regimen ................................................................................ 25 
6.1 
Description ........................................................................................................ 25 
6.2 
Instructions for Use and Application ................................................................ 25 
6.3 
Warnings, Precautions, and Contraindications ................................................. 26 
6.3.1 
Contraindications ....................................................................................... 26 
6.3.2 
Warnings .................................................................................................... 26 
6.3.3 
Precautions................................................................................................. 27 
6.3.4 
Adverse Events with Use of Topical Clindamycin ................................... 28 
7. 
Randomization Assignment .............................................................................. 28 
8. 
Prior and Concomitant Therapies ..................................................................... 28 
8.1 
Prohibited Medications or Therapies ................................................................ 29 
8.2 
Allowed Medications or Therapies ................................................................... 30 
9. 
Study Procedures .............................................................................................. 31 
9.1 
Visit 1 (Day 1): Screening/Baseline ................................................................. 31 
9.2 
Visit 2 (Day 15 ± 3): Follow-Up Telephone Call ............................................. 32 
9.3 
Visits 3 and 4 (Week 4/Day 29 ± 3 and Week 8/Day 57 ± 4): Follow-Up ....... 32 
9.4 
Visit 5 (Week 12/Day 85 ± 4): End of Study or Early Termination ................. 33 
9.5 
Unscheduled Visit ............................................................................................. 33 
10. 
Clinical Evaluations .......................................................................................... 34 
10.1 
Investigator’s Global Assessment ..................................................................... 34 
10.2 
Acne Lesion Counts .......................................................................................... 34 
10.3 
Safety Evaluations ............................................................................................ 35 
10.3.1 
Adverse Events .......................................................................................... 35 
10.3.2 
Local Skin Reactions ................................................................................. 35 


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Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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10.3.3 
Vital Signs ................................................................................................. 35 
10.3.4 
Urine Pregnancy Tests ............................................................................... 35 
10.3.5 
Concomitant Medications and Concurrent Procedures/Therapies ............ 36 
11. 
Photography ...................................................................................................... 36 
12. 
Laboratory Tests ............................................................................................... 36 
12.1 
Urine Pregnancy Tests ...................................................................................... 36 
13. 
End of Study Criteria ........................................................................................ 36 
13.1 
Completion of the Study ................................................................................... 36 
13.2 
Subject Discontinuation .................................................................................... 37 
13.3 
Study Termination ............................................................................................ 37 
14. 
Adverse Event Reporting .................................................................................. 38 
14.1 
Adverse Event Definitions ................................................................................ 38 
14.2 
Adverse Event Details....................................................................................... 39 
14.3 
Serious Adverse Event ...................................................................................... 40 
14.4 
Laboratory Test Abnormalities ......................................................................... 42 
14.5 
Pregnancy .......................................................................................................... 42 
15. 
Blinding/Unblinding ......................................................................................... 43 
16. 
Clinical Supplies ............................................................................................... 43 
16.1 
Test Article Information ................................................................................... 43 
16.2 
Supplies Provided by Therapeutics, Inc............................................................ 43 
16.3 
Supplies Provided by Investigator .................................................................... 44 
16.4 
Supplies Provided by Gage Development Company, LLC .............................. 44 
17. 
Statistical Considerations .................................................................................. 44 
17.1 
Sample Size ....................................................................................................... 44 
17.2 
Endpoints .......................................................................................................... 44 
17.2.1 
Efficacy Endpoints .................................................................................... 44 
17.2.2 
Safety Endpoints ........................................................................................ 44 
17.3 
Statistical Methods ............................................................................................ 45 
17.3.1 
Dosing Compliance ................................................................................... 45 
17.3.2 
Efficacy Analyses ...................................................................................... 45 
17.3.2.1 
Primary Efficacy Analyses .................................................................. 45 
17.3.2.2 
Exploratory Efficacy Analysis............................................................. 46 
17.3.2.3 
Imputation of Missing Data ................................................................. 46 
17.3.2.4 
Sensitivity Analysis ............................................................................. 46 
17.3.2.5 
Multiple Comparisons / Multiplicity ................................................... 46 
17.3.3 
Safety Analyses ......................................................................................... 46 
17.3.3.1 
Adverse Events .................................................................................... 46 
17.3.3.2 
Local Skin Reactions ........................................................................... 47 
17.4 
Subgroup Analyses ........................................................................................... 47 
17.5 
Interim Analyses ............................................................................................... 47 
18. 
Ethical and Regulatory Considerations ............................................................. 47 
18.1 
Compliance with Good Clinical Practice .......................................................... 47 
18.2 
Institutional Review Board and Informed Consent .......................................... 47 
18.3 
Protocol Compliance ......................................................................................... 48 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
18.4 
Protocol Revisions ............................................................................................ 48 
18.5 
Study Monitoring .............................................................................................. 48 
18.6 
Case Report Form Requirements ...................................................................... 49 
18.7 
Reports to Institutional Review Board .............................................................. 49 
18.8 
Quality Assurance Audits ................................................................................. 49 
18.9 
Records Retention ............................................................................................. 49 
18.10 Record Confidentiality ...................................................................................... 50 
19. 
References ......................................................................................................... 51 
Appendix 1 
Sample Subject Instruction Sheet .............................................................. 52 
Appendix 2 
Sample Subject Diary ................................................................................ 54 
Appendix 3 
Test Article Information ............................................................................ 56 
A 3.1 Test Article Packaging and Labeling ................................................................ 56 
A 3.2 Test Article Storage and Preparation ................................................................ 56 
A 3.3 Dispensing Test Article..................................................................................... 56 
A 3.4 Test Article Supply Records at Study Sites ...................................................... 57 
A 3.5 Dose Modifications ........................................................................................... 57 
A 3.6 Documentation of Application and Compliance............................................... 58 
A 3.7 Reserve Samples ............................................................................................... 58 
A 3.8 Return and Destruction of Test Article Supplies .............................................. 58 
Appendix 4 
Protocol Amendments ............................................................................... 59 
A 4.1 Protocol Amendment #1 ................................................................................... 59 
A 4.2 Protocol Amendment #2 ................................................................................... 63 


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Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
1. 
BACKGROUND 
Acne vulgaris (AV) is a chronic inflammatory dermatosis notable for open or closed 
comedones (blackheads and whiteheads) and inflammatory lesions, including papules, 
pustules, or nodules (also known as cysts). Lesions are most common on the face, but the 
neck, chest, upper back, and shoulders may also be affected. Acne is a common skin 
disease, especially in adolescents and young adults. Approximately 50 million people in 
the United States have AV [1]. Acne affects approximately 89% of teenagers, but can occur 
in most age groups [2] and can persist into adulthood.  
 
Acne is a multifactorial inflammatory disease affecting the pilosebaceous follicles of the 
skin. The current understanding of acne pathogenesis is continuously evolving. Key 
pathogenic factors that play an important role in the development of acne are follicular 
hyperkeratinization, microbial colonization with Propionibacterium acnes, sebum 
production, and complex inflammatory mechanisms involving both innate and acquired 
immunity. In addition, studies have suggested that neuroendocrine regulatory mechanisms, 
diet, and genetic and nongenetic factors all may contribute to the multifactorial process of 
acne pathogenesis [3]. 
 
Topical clindamycin is commonly used to treat acne. Clindamycin belongs to a class of 
medications called lincomycin antibiotics. It works by slowing or stopping the growth of 
bacteria that cause acne and by decreasing swelling. Clindamycin has a primarily 
bacteriostatic effect. It is a bacterial protein synthesis inhibitor that inhibits ribosomal 
translocation, in a similar way to macrolides. It does so by binding to the 50S rRNA of the 
large bacterial ribosome subunit, overlapping with the binding sites of the oxazolidinone, 
pleuromutilin, and macrolide antibiotics, among others. Topical clindamycin is available 
in several formulations: a foam, a gel, a solution (liquid), a lotion, and a pledget (swab) to 
apply to the skin.  
 
Clindamycin Phosphate Topical Lotion, 1% (Cleocin T) was approved by the FDA in 1989 
for the topical treatment of acne vulgaris. The reference product is currently available as 
an authorized generic product (GREENSTONE® BRAND). The FDA-approved regimen 
for the treatment of acne vulgaris is application of clindamycin phosphate topical lotion, 
1% twice daily to the affected area. A generic clindamycin phosphate topical lotion, 1% 
(GDC 268) has been developed by Gage Development Company, LLC for the topical 
treatment of acne vulgaris. 
2. 
RATIONALE 
Gage Development Company, LLC has developed GDC 268, a generic clindamycin 
phosphate topical lotion, 1% formulation, and the current clinical study is designed to 
evaluate the therapeutic equivalence of this formulation with the currently marketed 
Clindamycin Phosphate Topical Lotion, 1% (GREENSTONE® BRAND), the reference 
product. The dosage form, dosing frequency, treatment duration, and study design are 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 20 of 66 
 
CONTROLLED & CONFIDENTIAL 
consistent with the Reference Product package insert and with the FDA Office of Generic 
Drugs recommendation for a bioequivalence study with a clinical endpoint in the treatment 
of acne vulgaris with topical clindamycin phosphate lotion, 1% [4]. 
3. 
OBJECTIVE 
The objective of the study is to evaluate the safety, tolerability, and therapeutic equivalence 
of GDC 268 to Clindamycin Phosphate Topical Lotion, 1% and to compare the efficacy of 
these two products to the GDC vehicle lotion (i.e., placebo) in the treatment of acne 
vulgaris. 
4. 
STUDY DESIGN 
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group 
comparison study of GDC 268 and Clindamycin Phosphate Topical Lotion, 1% 
(GREEENSTONE® BRAND) in healthy male and non-pregnant, non-breastfeeding female 
subjects 12 to 40 years of age (inclusive) with facial acne vulgaris. Eligible subjects must 
have a clinical diagnosis of facial acne vulgaris with an Investigator’s Global Assessment 
(IGA) score of at least 2 (mild), a minimum of 25 but no more than 100 non-inflammatory 
lesions (open and closed comedones), a minimum of 20 but no more than 70 inflammatory 
lesions (papules and pustules) and ≤2 nodulocystic lesions (nodules and cysts) on the face 
at Baseline. Approximately 1200 subjects will be enrolled at approximately 50 study sites. 
Subjects will be randomized to one of three treatment groups on a 2:2:1 basis as follows:  
 
1. GDC 268 (Gage) (generic clindamycin phosphate topical lotion) 
2. Clindamycin Phosphate Topical Lotion, 1% (GREEENSTONE® BRAND) 
(Reference Product) 
3. GDC Vehicle (Gage) 
 
All subjects will be instructed to apply the assigned test article twice daily to the entire 
face, once in the morning and once in the evening, for 12 weeks. The study will consist of 
a Screening/Baseline Visit, a follow-up telephone call at Week 2, and follow-up visits at 
Weeks 4, 8, and 12/End of Study (EOS) or Early Termination (ET). An unscheduled in-
office follow-up visit may be completed at the discretion of the investigator for subjects 
with tolerability issues or a material adverse event (AE) concern. At EOS, safety and 
efficacy outcome measures will be compared to a) determine if treatment with GDC 268 is 
clinically equivalent to the currently marketed Clindamycin Phosphate Topical Lotion, 1% 
and b) both clindamycin phosphate 1% topical lotions are statistically superior in 
comparison to the GDC Vehicle. 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
5. 
STUDY POPULATION 
5.1 
Subject Eligibility 
To be included in the study, subjects must meet the following inclusion and none of the 
exclusion criteria. 
5.1.1 Inclusion Criteria 
1. Subject is a healthy male or non-pregnant, non-breastfeeding female 12 to 40 years of 
age (inclusive) at the time of consent/assent.  
2. Subject has provided written informed consent/assent. A subject under 18 years of age 
must provide written informed assent and be accompanied by the parent or legal 
guardian at the time of assent/consent signing. The parent or legal guardian must 
provide informed consent for the subject. If a subject becomes 18 years of age during 
the study, the subject must provide written informed consent at that time to continue 
study participation. 
3. Subject has a clinical diagnosis of mild to severe facial acne vulgaris defined as Grade 
2, 3, or 4 on the IGA at Baseline. 
4. Subject must have ≥ of 25 but ≤ 100 non-inflammatory lesions (open and closed 
comedones) AND ≥ 20 but ≤ 70 inflammatory lesions (papules and pustules) AND ≤ 2 
nodulocystic lesions (nodules and cysts) on the face (e.g., forehead, nose, cheeks, chin, 
upper lip) at Baseline. 
5. Subject and parent/guardian (if applicable) are willing and able to apply the test 
article(s) as directed, comply with study instructions, and commit to all follow-up visits 
for the duration of the study. 
6. Subject must be willing and able to refrain from use of all other topical products in the 
Treatment Area, all acne medications other than test article, and all antibiotics (other 
than test article) during the 12-week treatment period. 
7. Subject, in the investigator’s opinion, is in good general health and free of any disease 
state or physical condition that might impair evaluation of facial acne vulgaris or 
otherwise impact the integrity of the study, or exposes the subject to an unacceptable 
risk by study participation.  


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Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
8. Females must surgically sterile6 or use an effective method of birth control.7,8 Women 
of childbearing potential (WOCBP) must have a negative urine pregnancy test (UPT)9 
at Baseline.  
9. Subject has used the same type and brand of make-up, cleanser or other non-medicated 
facial products and hair products (e.g., Clinique foundation, Cetaphil soap, shampoo, 
hair gel, hairspray, mousse, etc.) for at least 4 weeks prior to Visit 1/Baseline and agrees 
to continue and not change his/her other general skin care and hair care products and 
regimen for the entire study. NOTE: Subjects who change from using a medicated acne 
cleanser that contains benzoyl peroxide, salicylic acid, etc. to using a bland non-
medicated/non-acne cleanser prior to Visit 1/Baseline will only be required to have 
used the new non-acne cleanser for at least 2 weeks in order to establish a stable skin 
care regimen. 
5.1.2 Exclusion Criteria 
1. Subject is pregnant, breastfeeding, or is planning to become pregnant or breastfeed 
during the study. 
2. Subject has active nodulocystic acne or acne conglobata, acne fulminans, or other 
forms of acne (e.g., acne mechanica). 
3. Subject has more than 2 facial nodules/cysts (where nodule/cyst is defined as an 
inflammatory lesion greater than or equal to 0.5 cm in size with or without cystic 
changes). 
4. Subject has any skin condition that, in the investigator’s opinion, could 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).  
                                                 
 
6 Hysterectomy, bilateral tubal ligation (at least 6 months prior to initiation of treatment), or bilateral 
oophorectomy. 
7 Effective forms of birth control include a) hormonal contraceptives [e.g., oral, transdermal, injectable, 
implantable, or vaginal ring] (see next footnote), b) intrauterine device (IUD), c) barrier methods [condom 
and spermicidal or diaphragm/cervical cap and spermicidal], d) monogamous relationship with a partner who 
is sterile [e.g., vasectomy performed at least 6 months prior to study entry], or e) total abstinence for subjects 
who are not sexually active. Subjects who become sexually active or begin to have relations with a partner 
of the opposite sex who is not sterile during the study must agree to use an effective form of birth control for 
the duration of the study.  
8 WOCBP taking hormonal therapy (e.g., oral, transdermal, injectable, implantable, vaginal ring) must be on 
treatment prior to study entry, continued per label, and must not change their dosing regimen during the 
study. WOCBP taking hormonal therapy for any reason must be on the same treatment for at least 3 
months prior to study entry. Those who have used hormonal therapy prior to study entry must have 
discontinued use at least 8 weeks prior to the start of the study. NOTE: Subjects using hormonal therapy for 
acne management should not be allowed to enroll unless they have washed out for at least 8 weeks prior to 
study entry. 
9 UPT must have a minimum sensitivity of 25 mIU ß-hCG/mL. 


Product Name: GDC 268 
 
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CONTROLLED & CONFIDENTIAL 
5. Subject has excessive facial hair (e.g., beards, sideburns, moustaches, etc.), facial 
tattoos, or other facial attributes that would interfere with diagnosis or assessment of 
acne vulgaris in the opinion of the investigator. 
6. Subject has a history of hypersensitivity or allergy to clindamycin or lincomycin and/or 
any of the ingredients in the test articles (see Section 6.1). 
7. Subject has a history of regional enteritis or ulcerative colitis, or a history of antibiotic-
associated colitis. 
8. Subject is atopic (e.g., atopic dermatitis, allergic rhinitis, allergic asthma). Note: 
Subjects that are not atopic but have a component(s) of this syndrome may be enrolled 
(e.g., a person with allergic rhinitis or allergic asthma). 
9. Subject has used any of the following topical preparations or procedures on the face: 
 Topical retinoids (e.g., tazarotene, adapalene, and tretinoin) within 2 weeks prior 
to Baseline; 
 Topical anti-acne treatments including, but not limited to, over-the-counter 
(OTC) acne cleansers, soaps, washes or treatments, benzoyl peroxide, antibiotics, 
azelaic acid, dapsone, sulfa based products, corticosteroids, and salicylic acid 
within 2 weeks prior to Baseline; 
 Topical steroids within 2 weeks prior to Baseline. 
 Topical antibiotics within 2 weeks prior to Baseline. 
 Topical anti-inflammatory agents within 2 weeks prior to Baseline; 
 Cryodestruction or chemodestruction, dermabrasion, photodynamic therapy 
including other light-based and laser therapies, acne surgery, intralesional 
steroids, or x-ray therapy within 4 weeks prior to Baseline; 
 Other topical therapy, which may materially affect the subject’s acne, in the 
investigator’s opinion. 
10. Subject has used any of the following systemic medications: 
 Corticosteroids (including intramuscular, intra-articular, and intralesional 
injections) for any indication within 4 weeks prior to Baseline; 
 Antibiotics10 for any indication or other systemic anti-acne medications within 4 
weeks prior to Baseline; 
 Androgen receptor blockers (e.g., spironolactone, flutamide) within 4 weeks 
prior to Baseline; 
 Retinoid therapy (e.g., isotretinoin) within 6 months prior to Baseline; 
 Vitamin A supplements (greater than 10,000 units per day) within 6 months prior 
to Baseline; 
 Anti-inflammatory agents or immunosuppressive drugs within 4 weeks prior to 
Baseline; 
 Neuromuscular blocking agents such as botulinum toxin type A (e.g., BOTOX, 
DYSPORT) within 2 weeks prior to Baseline; 
                                                 
 
10 Contact the Medical Monitor if a subject requires concomitant antibiotic therapy. 


Product Name: GDC 268 
 
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Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
 Other systemic therapy, which may materially affect the subject’s acne, in the 
investigator’s opinion. 
11. Subject has used oral contraceptives or estrogen for less than 3 months prior to 
Baseline. 
12. Subject is planning surgery during the study. 
13. Subject has the need or plans to be exposed to artificial tanning devices or excessive 
sunlight during the study. 
14. Subject is currently enrolled in an investigational drug, device, or biologic study. 
15. Subject has used an investigational drug or investigational device treatment within 30 
days prior to first application of the test article. 
16. Subject is known to be noncompliant or is unlikely to comply with the requirements of 
the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the 
opinion of the investigator.  
17. Subject and parent/guardian (if applicable) are unable to communicate or cooperate 
with the investigator due to language problems, poor mental development, or impaired 
cerebral function. 
5.1.3 Subject Withdrawal Criteria 
Procedures for handling subjects who are discontinued from the study are described in 
Section 13.2. Subjects who are discontinued will not be replaced. 
5.1.4 Enrollment of Protected Population 
Employees of the study site will be allowed to participate in this study if they wish to do 
so only if they are not involved with the conduct of this study and do not have access to 
study materials or documents. Family members of employees of the study site will also be 
allowed to participate in this study if they wish to do so and if they meet all of the inclusion 
and none of the exclusion criteria. Both employees and their family members are 
considered a protected population which requires the study site to obtain and use a modified 
informed consent/assent from the Institutional Review Board (IRB). Special care will be 
taken to ensure the following: 
 
For an employee, the decision to participate or not participate will NOT affect: 
 performance evaluations, 
 possible promotions, and 
 salary or benefits. 
 
For a family member of an employee, the decision to participate or not participate will 
NOT affect the employee’s: 
 performance evaluations, 
 possible promotions, and 
 salary or benefits. 


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Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
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CONTROLLED & CONFIDENTIAL 
5.1.5 Subjects from the Same Household 
Subjects from the same household will be allowed to participate in this study; however, no 
more than 2 subjects may be enrolled from the same household. Ideally, these subjects 
should not be enrolled in the study at the same time. If 2 subjects from the same household 
are enrolled concurrently, every effort shall be made to keep all test article and study 
documents (e.g., subject diaries) separate for each subject. Sites should carefully review 
each subject’s returned test article at each visit and question each subject as to whether they 
only used the test article assigned to them. 
6. 
TEST ARTICLES AND REGIMEN 
The test articles used in this study are described below. 
6.1 
Description 
Reference product: 
 
Clindamycin Phosphate Topical Lotion, 1% 
(GREEENSTONE® BRAND) 
Active ingredient: 
 
Clindamycin phosphate 
Other ingredients: 
Cetostearyl alcohol; glycerin; glyceryl stearate SE (with 
potassium 
monostearate); 
isostearyl 
alcohol; 
methylparaben; sodium lauroyl sarcosinate; stearic acid; and 
purified water. 
 
Test product:  
 
GDC 268 (Gage) 
Active ingredient: 
 
Clindamycin phosphate 
Other ingredients: 
Cetostearyl alcohol; glycerin; glyceryl stearate SE (with 
potassium 
monostearate); 
isostearyl 
alcohol; 
methylparaben; sodium lauroyl sarcosinate; stearic acid; and 
purified water. 
 
Placebo: 
 
 
GDC Vehicle (Gage) 
Active ingredient: 
 
None 
Other ingredients: 
Cetostearyl alcohol; glycerin; glyceryl stearate SE (with 
potassium 
monostearate); 
isostearyl 
alcohol; 
methylparaben; sodium lauroyl sarcosinate; stearic acid; and 
purified water. 
6.2 
Instructions for Use and Application 
At the Baseline Visit, the subject and parent/guardian (if applicable) will be instructed on 
how to apply the test article and, as part of training, the subject will apply the non-
medicated sample in the clinic under staff supervision to ensure proper application. The 
bottle of test article should be shaken well immediately before each application. A disc 
about the size of a quarter of the test article will be dispensed and the test article will be 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 26 of 66 
 
CONTROLLED & CONFIDENTIAL 
applied using the fingertip by gently dabbing small amounts to the entire face (inclusive; 
i.e., forehead, nose, cheeks, chin, upper lip) and spreading the test article in a thin, uniform 
layer across the entire face, not just on individual lesions, with each application.  
 
Subjects will be instructed to apply the test article to the entire face twice daily, once in the 
morning and once in the evening, with approximately 8 to 12 hours in between applications 
for 12 weeks with the first dose of test article to be applied on the evening of the Baseline 
Visit. Note: Subjects who have an alternate sleep-wake schedule may adjust their twice 
daily dosing according to their schedule as long as their twice daily applications are 
approximately 8 to 12 hours apart. Subjects should not wash the treated area for at least 4 
hours following test article application and should not apply the test article within 4 hours 
before any study visit. After test article application, allow a 10 minute dry-down period 
before applying any other approved facial product. 
 
Subjects will be provided with a Subject Instruction Sheet detailing how to apply the test 
article (see Appendix 1) and a Subject Diary (see Appendix 2) to record dates and times of 
applications and any missed doses. Subjects will be instructed to bring all test article bottles 
(used and unused) and the Subject Diary to each study visit. At each visit, the Subject Diary 
will be collected, reviewed, and a new one will be provided to the subject (as needed).  
6.3 
Warnings, Precautions, and Contraindications 
The safety information in this section is derived from the US Prescribing Information for 
Clindamycin Phosphate Topical Lotion, 1% reference product (GREEENSTONE® 
BRAND). 
6.3.1 Contraindications 
Clindamycin phosphate topical lotion is contraindicated in subjects with a history of 
hypersensitivity to preparations containing clindamycin or lincomycin, a history of 
regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis. 
6.3.2 Warnings 
Orally and parenterally administered clindamycin has been associated with severe colitis 
which may result in patient death. Use of the topical formulation of clindamycin results in 
absorption of the antibiotic from the skin surface. Diarrhea, bloody diarrhea, and colitis 
(including pseudomembranous colitis) have been reported with the use of topical and 
systemic clindamycin. 
 
Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic-
associated colitis. The colitis is usually characterized by severe persistent diarrhea and 
severe abdominal cramps and may be associated with the passage of blood and mucus. 
Endoscopic examination may reveal pseudomembranous colitis. Stool culture for 
Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically. 


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When significant diarrhea occurs, the test article should be discontinued. Large bowel 
endoscopy should be considered to establish a definitive diagnosis in cases of severe 
diarrhea. 
 
Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or 
worsen the condition. Vancomycin has been found to be effective in the treatment of 
antibiotic-associated pseudomembranous colitis produced by C. difficile. The usual adult 
dosage is 500 milligrams to 2 grams of vancomycin orally per day in 3 to 4 divided doses 
administered for 7 to 10 days. Cholestyramine or colestipol resins bind vancomycin in 
vitro. If both a resin and vancomycin are to be administered concurrently, it may be 
advisable to separate the time of administration of each drug. 
 
Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several 
weeks following cessation of oral and parenteral therapy with clindamycin. 
6.3.3 Precautions 
General 
Clindamycin phosphate topical products should be prescribed with caution in atopic 
individuals. 
 
Drug Interactions 
Clindamycin has been shown to have neuromuscular blocking properties that may enhance 
the action of other neuromuscular blocking agents. Therefore it should be used with caution 
in patients receiving such agents. 
 
Pregnancy 
Teratogenic effects 
In clinical trials with pregnant women, the systemic administration of clindamycin during 
the second and third trimesters has not been associated with an increased frequency of 
congenital abnormalities. There are no adequate studies in pregnant women during the first 
trimester of pregnancy. Clindamycin should be used during the first trimester of pregnancy 
only if clearly needed. 
 
Nursing Mothers 
It is not known whether clindamycin is excreted in human milk following use of 
clindamycin phosphate. However, orally and parenterally administered clindamycin has 
been reported to appear in breast milk. Clindamycin has the potential to cause adverse 
effects on the breastfed infant's gastrointestinal flora. If oral or intravenous clindamycin is 
required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate 
drug may be preferred. Monitor the infant for possible adverse effects on the 
gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in 
the stool indicating possible antibiotic-associated colitis. 


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The developmental and health benefits of breastfeeding should be considered along with 
the mother's clinical need for clindamycin and any potential adverse effects on the breastfed 
child from clindamycin or from the underlying maternal condition. 
6.3.4 Adverse Events with Use of Topical Clindamycin 
Per the Reference Product package insert, in 18 clinical studies of various formulations of 
clindamycin phosphate using placebo vehicle and/or active comparator drugs as controls, 
patients experienced a number of treatment emergent adverse dermatologic events 
including burning, itching, dryness, erythema, oiliness/oily skin, and peeling. Abdominal 
pain, gastrointestinal disturbances, gram-negative folliculitis, eye pain, and contact 
dermatitis have also been reported in association with the use of topical formulations of 
clindamycin. 
7. 
RANDOMIZATION ASSIGNMENT 
Subjects will be randomized on a 2:2:1 basis to one of three treatment groups: 
1. GDC 268 (Test) 
2. Clindamycin Phosphate Topical Lotion, 1% (Reference Product) 
3. GDC Vehicle (Placebo) 
 
The study will use a central randomization scheme and stratified by the number of non-
inflammatory lesions (≤70 / > 70) present at the Baseline visit. Subjects who are eligible 
for enrollment into the study will be randomized at Visit 1/Baseline; subject kits will be 
dispensed according to the kit number assigned by an Interactive Web Response System 
(IWRS) as subjects are enrolled. Treatment group designation will remain blinded until the 
final database is locked (see Section 15). 
 
A sealed copy of the randomization scheme should be retained at the study site and should 
be available to FDA investigators at the time of site inspection to allow for verification of 
the treatment identity of each subject. 
8. 
PRIOR AND CONCOMITANT THERAPIES 
Current medications and any medications taken within 30 days prior to the start of the study 
(Baseline) will be recorded as prior/concomitant medications with the dose (in source 
documents only) and corresponding indication. The medications to be recorded include 
prescription, OTC medications, and vitamins, minerals, and dietary supplements being 
taken for a therapeutic indication. Vitamins and mineral supplements are permitted at 
dosages considered by the investigator as reasonable for maintaining good health and will not 
be recorded on the electronic case report forms (eCRFs). All concomitant medications will 
be coded with the current version of the WHO Drug Dictionary. 
 


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Any changes in concomitant medications and/or procedures/therapies during the study must 
be recorded. The reason for any changes in concomitant medications and/or 
procedures/therapies should be reported and should reflect either a baseline medical 
condition documented in the medical history or in conjunction with an AE. 
8.1 
Prohibited Medications or Therapies 
Subjects must not use the medications or procedures in the timeframe noted below.  
 
Within 24 hours of study visits during the study: 
 Antipruritics, including antihistamines. 
 
Within 2 weeks prior to Baseline and during the study: 
 Topical retinoids (e.g., tazarotene, adapalene, and tretinoin) on the face; 
 Topical anti-acne treatments including, but not limited to, OTC acne cleansers, 
soaps, washes or treatments, benzoyl peroxide, antibiotics, azelaic acid, dapsone, 
sulfa based products, corticosteroids, and salicylic acid on the face; 
 Topical steroids on the face; 
 Topical antibiotics on the face; 
 Topical anti-inflammatory agents on the face; 
 Neuromuscular blocking agents such as botulinum toxin type A (e.g., BOTOX, 
DYSPORT) at any body site. 
 
Within 30 days prior to Baseline and during the study: 
 Investigational drugs, devices, or biologics. 
 
Within 4 weeks prior to Baseline and during the study: 
 Cryodestruction or chemodestruction, dermabrasion, photodynamic therapy 
including other light-based and laser therapies, acne surgery, intralesional steroids, 
or x-ray therapy on the face; 
 Systemic corticosteroids (including intramuscular, intra-articular, and intralesional 
injections) for any indication; 
 Systemic antibiotics11 for any indication or other systemic anti-acne medications; 
 Androgen receptor blockers (e.g., spironolactone, flutamide); 
 Anti-inflammatory agents or immunosuppressive drugs. 
 
Within 6 months prior to Baseline and during the study: 
 Systemic retinoid therapy (e.g., isotretinoin); 
 Vitamin A supplements (greater than 10,000 units per day). 
 
                                                 
 
11 Contact the Medical Monitor if a subject requires concomitant antibiotic therapy. 


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During the study, the following are prohibited: 
 Any other topical or systemic therapy, which may materially affect the subject’s 
acne, in the investigator’s opinion; 
 Exposure to excessive sunlight or artificial tanning devices. 
8.2 
Allowed Medications or Therapies 
Contraception for WOCBP is required per Inclusion Criterion #8 (see Section 5.1.1). 
Vitamins and mineral supplements are permitted at dosages considered by the investigator 
as reasonable for maintaining good health and will not be recorded in the eCRFs. 
 
Subjects must be on a consistent skin care regimen for at least 4 weeks prior to 
Visit 1/Baseline and must not alter the regimen for the entire study. NOTE: Subjects who 
change from using a medicated acne cleanser that contains benzoyl peroxide, salicylic acid, 
etc. to using a bland non-medicated/non-acne cleanser prior to Visit 1/Baseline will only 
be required to have used the new non-acne cleanser for at least 2 weeks in order to establish 
a stable skin care regimen. Allowed skin care products include any type or brand of make-
up, cleanser, non-medicated facial product, or hair product (e.g., Clinique foundation, 
Cetaphil soap, shampoo, hair gel, hairspray, mousse). General skin/hair care products (e.g., 
shampoo, hairspray, Cetaphil soap) and minimal use of non-medicated facial products and 
make-up (e.g., light powder, light foundation, lip stick, mascara, sunscreen) is permitted 
after test article application and a 10-minute dry-down period, provided that the subject has 
been using the products for at least 4 weeks prior to Visit 1/Baseline. Changes in the use 
of type or brand of eyeliner for use on the eyes, lipstick, and/or mascara for the eyelashes 
are allowed prior to and during the study since these products do not involve facial areas 
typically affected by acne and thus, do not materially impact the Treatment Area. These 
and other allowed skin care products do not need to be recorded in the eCRFs. With respect 
to sunscreen, if sunscreen is not part of the subject’s stable skin care regimen, sunscreen 
may be used in the Treatment Area for significant sun exposure events (e.g., out on a boat 
all day); however, such use of sunscreen should be listed as a concomitant medication or 
therapy and recorded in the eCRFs. 
 
Therapies (medication and non-medication therapies) not restricted by the protocol may be 
used during the study for the treatment or prevention of disease or to maintain good health.  
 
Non-prohibited chronic therapies being used at Visit 1/Baseline may be continued, but must 
be recorded. 
 
Intranasal steroids as well as inhaled (puffer) or ophthalmic steroid preparations are allowed. 
 
Reasonable use of OTC medications such as NSAIDs (e.g., aspirin, ibuprofen) or 
analgesics or antipyretics (e.g., acetaminophen) for relief of headache, muscle ache, etc. is 
allowed during the study and must be recorded. 


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9. 
STUDY PROCEDURES 
Specific activities for each study visit are listed below. 
9.1 
Visit 1 (Day 1): Screening/Baseline 
At Screening, the investigator or qualified designee will: 
 Obtain a signed, written informed consent/assent. 
 Record subject demographics. 
 Review inclusion/exclusion (I/E) criteria and confirm subject eligibility.  
 Record medical history. 
 Record prior and/or concomitant medications and procedures/therapies. 
 Have subject complete washout from any prohibited medications, if necessary. 
 
If the subject requires washout from previous medications, the remaining activities will be 
performed after washout is complete as a separate Baseline Visit. 
 If the washout requires longer than 45 days, re-consent/assent should occur.  
 Reconfirm I/E criteria and subject eligibility. 
 Perform a dermatological exam. 
 Measure vital signs (including temperature, systolic and diastolic blood pressure, 
heart rate, and respiration rate) and height and weight (see Section 10.3.3). 
 Perform a UPT for all WOCBP. The results must be negative for the subject to be 
enrolled. 
 Perform clinical evaluations: IGA (see Section 10.1) and acne lesion counts (see 
Section 10.2).  
 Assess LSRs (see Section 10.3.2). 
 Perform standardized photography of the face (see Section 11). 
 Randomize the subject and assign the subject kit according to the IWRS. 
 Document Test Article Accountability. Weigh test article prior to dispensing to 
subject and record baseline weight. 
 Demonstrate how to apply test article using the non-medicated samples provided to 
the site and have subject apply the non-medicated sample in the clinic under staff 
supervision to ensure proper application. Instruct the subject to apply the first dose 
on the evening of the Baseline Visit.  
 Review and dispense a Subject Instruction Sheet (see Appendix 1). 
 Dispense the Subject Diary and provide completion instructions (see Appendix 2). 
 Review allowed skin care products per Section 8.2. 
 Schedule a follow-up telephone call (Visit 2) and in clinic follow-up (Visit 3). 


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9.2 
Visit 2 (Day 15 ± 3): Follow-Up Telephone Call 
At this phone visit, the investigator or qualified designee will: 
 Query the subject about any changes in health status or any AEs since the last visit. 
Document in the AE section of the eCRF, as appropriate. NOTE: If severe 
tolerability issues or a material AE concern of any type are noted, the subject may 
be scheduled for an in-office visit at the investigator’s discretion. 
 Record 
any 
changes 
in 
the 
subject’s 
concomitant 
medications 
and 
procedures/therapies. 
 Review the Subject Diary and test article compliance.  
 Remind the subject to continue to apply test article twice daily to their entire face, 
once in the morning and once in the evening, until the next clinic visit and to bring 
all bottles (used and unused) of test article with him/her to the next clinic visit. 
 Confirm the next scheduled visit and remind the subject or parent/legal guardian (if 
applicable) not to apply test article or other products to the face within 4 hours prior 
to the next appointment.  
 Review allowed skin care products per Section 8.2. 
 Inquire if the subject has any other questions or needs; in the event the subject is 
having any issues with the test article or material health concerns, the investigator 
will determine if an unscheduled visit (see Section 9.5) or other measures are 
required. 
 Call the day prior to the next scheduled visit to remind subjects not to apply test 
article or other products to the face within 4 hours of the next visit. 
9.3 
Visits 3 and 4 (Week 4/Day 29 ± 3 and Week 8/Day 57 ± 4): Follow-Up 
At this visit, the investigator or qualified designee will: 
 Query the subject about any changes in health status since the last visit. Document 
in the AE section of the eCRF, as appropriate.  
 Record 
any 
changes 
in 
the 
subject’s 
concomitant 
medications 
and 
procedures/therapies. 
 Perform clinical evaluations: IGA (see Section 10.1) and acne lesion counts (see 
Section 10.2).  
 Assess LSRs (see Section 10.3.2).  
 Document Test Article Accountability. The subject’s new and used test article will 
be weighed and re-dispensed as necessary. 
 Collect, review, and distribute the Subject Diary as necessary. 
 Review test article compliance. Test article application will be demonstrated if 
deemed necessary. 
 Remind the subject to continue to apply test article twice daily to their entire face, 
once in the morning and once in the evening, until the next clinic visit and to bring 
all bottles (used and unused) of test article with him/her to the next clinic visit. 


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 Schedule the next visit and remind the subject or parent/legal guardian (if 
applicable) not to apply test article or other products to the face within 4 hours prior 
to the next appointment.  
 Review allowed skin care products per Section 8.2. 
 Call the day prior to the next scheduled visit to remind subjects not to apply test 
article or other products to the face within 4 hours of the next visit.  
9.4 
Visit 5 (Week 12/Day 85 ± 4): End of Study or Early Termination 
At this visit, the investigator or qualified designee will: 
 Query the subject about any changes in health status or any AEs since the last visit. 
Document in the AE section of the eCRF, as appropriate.  
 Record 
any 
changes 
in 
the 
subject’s 
concomitant 
medications 
and 
procedures/therapies. 
 Perform a UPT for all WOCBP. 
 Perform clinical evaluations: IGA (see Section 10.1) and acne lesion counts (see 
Section 10.2).  
 Assess LSRs (see Section 10.3.2).  
 Document Test Article Accountability. Weigh and collect all test articles. 
 Collect and review the Subject Diary and determine test article compliance.  
 The subject will exit the study.  
9.5 
Unscheduled Visit 
An unscheduled in-office follow-up visit may be completed at the discretion of the 
investigator for subjects with tolerability issues or a material AE concern. 
 
At this visit, the investigator or qualified designee will: 
 Query the subject about any changes in health status or any AEs since the last visit. 
Document in the AE section of the eCRF, as appropriate.  
 Record 
any 
changes 
in 
the 
subject’s 
concomitant 
medications 
and 
procedures/therapies. 
 Assess LSRs, if applicable (see Section 10.3.2).  
 Review the Subject Diary and test article compliance.  
 Remind the subject to continue to apply test article twice daily, once in the morning 
and once in the evening, until the next clinic visit and to bring all bottles (used and 
unused) of test article with him/her to the next clinic visit. 
 Confirm the next scheduled visit and remind the subject or parent/legal guardian (if 
applicable) not to apply test article or other products to the face within 4 hours prior 
to the next appointment.  
 Review allowed skin care products per Section 8.2. 
 Call the day prior to the next scheduled visit to remind subjects not to apply test 
article or other products to the face within 4 hours of the next visit.  




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Non-inflammatory lesions: 
 Comedones: open (blackheads) and closed (whiteheads). 
 
Inflammatory lesions: 
 Papules: raised inflammatory lesions with no visible purulent material. 
 Pustules: raised inflammatory lesions with visible purulent material. 
 
Nodulocystic lesions: 
 Nodules and cysts: any circumscribed, inflammatory masses greater or equal to 
5 mm in diameter with or without cystic changes. 
10.3 
Safety Evaluations 
10.3.1 Adverse Events 
All reported or observed AEs will be recorded. At each visit, subjects will also be 
questioned specifically about the status of any ongoing AEs. Untoward events that occur 
prior to the first dose of test article will be captured in the Medical History section of the 
eCRF unless they are related to a study-specific procedure. See Section 14 for details on 
Adverse Event Reporting.  
10.3.2 Local Skin Reactions 
At each visit, LSRs (erythema, edema, scaling/dryness, stinging/burning, pruritus, erosion, 
and pain) will be assessed. Erythema, edema, scaling/dryness, and erosion will be assessed 
by the investigator and stinging/burning, pain, and pruritus will be assessed by the subject. 
Assessments will be made using a 4-point ordinal scale where 0=absent, 1=mild (slight, 
barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). Only 
LSRs that require medical intervention (e.g., prescription medication), require withholding 
or discontinuation of the application of the test article, or extend 2 cm beyond the 
Treatment Area will be documented as AEs. Any LSR that are not listed above will be 
recorded as an AE. 
10.3.3 Vital Signs 
Vital signs including temperature, systolic and diastolic blood pressure, heart rate, and 
respiration rate will be measured at Visit 1/Baseline. Assessments will be made after the 
subject has rested in a seated position for at least 5 minutes. Height and weight will also be 
measured at Visit 1/Baseline. 
10.3.4 Urine Pregnancy Tests 
A UPT will be performed at Visit 1/Baseline and at Visit 5/Week 12/EOS for WOCBP. 


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10.3.5 Concomitant Medications and Concurrent Procedures/Therapies 
Concomitant medications and concurrent procedures/therapies will be reviewed at all visits 
and any changes will be recorded.  
11. 
PHOTOGRAPHY 
Photography documentation is required in this study so to participate in the study subjects 
must consent to photographs. Photographs taken as part of this study will be used to 
document the subject’s baseline disease, AEs, or other findings during the study. The site 
will be provided with suggested guidelines to assist them in taking standardized 
photographs of the face in 3 views (front, right, and left [45 degrees oblique for right and 
left]) at Baseline. All photographs taken as part of this study are for informational purposes 
only and are not to assist in grading or for any other assessment. Photographs will be 
compiled and reviewed and may be used to evaluate investigator/grader training needs, but 
no formal assessments will be performed.  
 
Note: Subjects who decline to have photographs taken during the conduct of study after 
Baseline may continue to participate in the study. If a subject initially consents to 
photographs, then declines further photography as/if required, the Sponsor may use the 
photographs taken under consent for the purposes noted above. 
 
Additional details regarding photographic methods, uploading and labeling photos etc. will 
be provided in a Photo Manual to the site. 
12. 
LABORATORY TESTS 
12.1 
Urine Pregnancy Tests 
The UPTs will be performed at the study site, if the site is registered and conforms to CLIA 
regulations for such testing (possesses a current valid CLIA Certificate of Waiver), or at 
an appropriately registered reference laboratory. The investigator will report the UPT 
results on the eCRFs, in the subject’s medical records, and in independent records 
maintained at the study site. The UPT used must have a minimum sensitivity of 25 mIU of 
-hCG/mL. 
13. 
END OF STUDY CRITERIA 
At the end of each subject’s participation in the study, the investigator will complete an 
EOS Disposition form for all completed and discontinued subjects.  
13.1 
Completion of the Study 
Subjects who complete the 12-week course of treatment as specified in this protocol will 
be considered to have completed the study. 


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13.2 
Subject Discontinuation 
A subject may be withdrawn from the study prior to completion for any of the following 
reasons: 
 AEs 
 Death 
 Lack of efficacy 
 Lost to follow-up 
 Non-compliance with test article 
 Physician decision 
 Pregnancy 
 Progressive disease 
 Protocol deviation 
 Study terminated by Sponsor 
 Withdrawal by subject; NOTE: if the subject decides to withdraw from the study 
due to an AE then it should be classified as withdrawal due to an AE 
 Other (e.g., any reason that may affect the outcome of the study or safety of 
subjects) 
 
If a randomized subject withdraws from the study prematurely for any reason, the site 
should make every effort to have the subject return to the clinic to perform all of the 
required visit activities and to collect and reconcile all test articles (if applicable). If the 
randomized subject will not return to the clinic, the site should make every attempt to 
contact the subject; otherwise the subject will be considered lost to follow-up.  
 
When a subject is withdrawn from the study for a test article related AE (as defined in 
Section 14.2), when possible, the subject should be followed until resolution or 
stabilization of the AE. If the subject is discontinued from the study due to pregnancy, the 
pregnancy and its outcome should be followed. 
 
Subjects who are prematurely withdrawn or discontinued from the study will not be 
replaced. 
13.3 
Study Termination 
The study may be terminated by the investigator or the Sponsor. If, in the opinion of the 
investigator, clinical observations made during the study suggest that it may be unwise to 
continue, he or she may stop the study. A study termination by the investigator will be 
reported to the Sponsor.  
 
In addition, a written statement fully documenting the reasons for this action will be 
submitted to the Sponsor by the investigator within 5 working days. 
 


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In the event that the Sponsor chooses to discontinue or terminate the study, appropriate 
notification will be given to the investigator. 
 
If the study is terminated for any reason subjects should be withdrawn from the study in an 
orderly manner following the steps outlined in Section 13.2. 
14. 
ADVERSE EVENT REPORTING 
14.1 
Adverse Event Definitions 
An adverse event is any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered test article related.  
 
An AE (also referred to as an adverse experience) can be any unfavorable and unintended 
sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of a drug, without any judgment about causality. An AE can arise from any use of 
the drug (e.g., off-label use, use in combination with any drug) and from any route of 
administration, formulation, or dose, including an overdose. 
 
A suspected adverse reaction is any AE for which there is a reasonable possibility that 
the drug caused the event. “Reasonable possibility” means there is evidence to suggest a 
causal relationship between the drug and the AE. 
 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions for which there is reason to conclude that the drug caused the 
event. A suspected adverse reaction implies a lesser degree of certainty about causality 
than adverse reaction, which means any AE caused by a drug. For the purposes of 
prescription drug labeling, the term adverse reaction means an undesirable effect, 
reasonably associated with the use of a drug that may occur as part of its pharmacological 
action or may be unpredictable in its occurrence.  
 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Reference Product package insert or is not listed at the specificity or severity that has been 
observed. For example, under this definition, hepatic necrosis would be unexpected (by 
virtue of greater severity) if the IB Reference Product package insert referred only to 
elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral 
vasculitis would be unexpected (by virtue of greater specificity) if the Reference Product 
package insert listed only cerebral vascular accidents. "Unexpected," as used in this 
definition, also refers to AEs or suspected adverse reactions that are mentioned in the 
Reference Product package insert as occurring with a class of drugs or as anticipated from 
the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation.  


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14.2 
Adverse Event Details 
AEs may be either spontaneously reported, observed, or elicited during questioning and 
examination of a subject. All AEs following the first dose of test article must be recorded 
on the AE eCRF. Any untoward events occurring prior to test article administration will be 
reported in the Medical History, unless related to a study-specific procedure. If known, the 
investigator should report the diagnosis of the underlying illness or disorder, rather than its 
individual symptoms. Subjects experiencing AEs that cause interruption or discontinuation 
of test article or those experiencing AEs that are present at the end of their participation in 
the study should receive follow-up as appropriate. AEs should be followed to resolution or 
stabilization (if possible) and, if they become serious, reported as serious adverse events 
(SAEs, see Section 14.3). If possible, the outcome of any AEs that caused permanent 
discontinuation or that were present at the end of the study, especially those considered by 
the investigator to be related to the test article, should be reported. 
 
Information on the medical condition of subjects should begin following the subject’s 
written informed consent/assent to participate in the study and a medical history should be 
taken at screening. During any wash out and baseline periods, any changes in the health of 
subjects should be recorded as changes in medical history unless an event occurred as a 
result of a study-related procedure and is unanticipated; in such cases, the event should be 
recorded as an AE and reported to the IRB as an “unanticipated problem” in accordance 
with local procedures. Other changes in subject health information becomes AE data when 
the subject begins dosing with the test article; therefore AE data should be collected from 
the date of the first dose of test article until the date of the final study visit. These data are 
considered treatment-emergent AEs. 
 
The investigator will instruct the subject to report any AEs that may occur during the study. 
At each visit, the investigator should ask the subject, in non-directive fashion, about any 
change in the subject’s overall health status since the previous visit. 
 
The severity of each AE, as judged by the investigator, will be recorded on the appropriate 
AE eCRF and will be graded according to the following scale: 
 
Mild - The AE is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities 
of daily living. 
 
Moderate - The AE is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort, but poses no significant or permanent risk of harm to the research 
participant. 
 
Severe - The AE interrupts usual activities of daily living or significantly affects 
clinical status, or may require intensive therapeutic intervention. 


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The investigator must determine the relationship of the AE to the test article according to 
the following categories: 
 
Related – There is a strong medical evidence to suggest that the AE is related to 
test article usage. 
 
Possibly Related – There is medical evidence to suggest that the AE may be related 
to test article usage. 
 
Not Related – There is no medical evidence to suggest that the AE may be related 
to test article usage. 
 
The investigator should categorize the outcome of the AE according to the following 
categories: 
 
Fatal - Termination of life as a result of an AE. 
 
Not Recovered/Not Resolved - AE has not improved or the subject has not 
recuperated. 
 
Recovered/Resolved - AE has improved or the subject has recuperated. 
 
Recovered/Resolved with Sequelae - subject recuperated but retained the 
pathological conditions resulting from the prior disease or injury. 
 
Recovering/Resolving - AE is improving or the subject is recuperating. 
 
Unknown - Not known, not observed, not recorded or subject refused. 
14.3 
Serious Adverse Event 
An event that is serious must be recorded on the AE eCRF and on the TI SAE Report Form, 
and requires expeditious handling to comply with regulatory requirements. 
 
An AE or suspected adverse reaction is considered “serious” if, in the opinion of either the 
investigator or Sponsor, it results in any of the following outcomes: 
 Death; the event must be the cause of death for the SAE to meet this serious 
criterion. 
 Life-threatening event; an event in which the subject was at risk of death at the time 
of the event and not an event that hypothetically might have caused death if it had 
been more severe. 
 Requires inpatient hospitalization or prolongation of existing hospitalization (for 
≥24 hours). 


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 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
 Congenital anomaly/birth defect. 
 Important medical events; a medical event(s) that may not result in death, be life-
threatening, or require hospitalization but, based upon appropriate medical 
judgment, may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in the definition above. Examples 
of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result 
in inpatient hospitalization, or the development of drug dependency or drug abuse.  
 
Events NOT considered to be SAEs are: 
 Hospitalizations for the treatment, which was elective or pre-planned, of a pre-
existing condition that did not worsen; and 
 Treatment on an emergency, outpatient basis, for an event not fulfilling any of the 
definitions of “serious” given above and not resulting in hospital admission. 
 
AEs classified as “serious” by either the investigator or the Sponsor require expeditious 
handling and reporting to TI to comply with regulatory requirements. All SAEs, whether 
related or unrelated to test article, must be reported as soon as possible but no later 
than 24 hours from when the event occurred by telephone to the Medical Monitor 
and, in the event that he is unavailable, to the Project Manager (see contact 
information below). Written notification of all SAEs should be sent to the Project 
Manager by email or confirmed facsimile transmission. These include those SAEs listed in 
the protocol or Reference Product package insert and must include an assessment of 
whether there is a reasonable possibility that the test article caused the event.  
 
Medical Monitor: 
 
 
 
 
) 
 
In the event the Medical Monitor is unavailable, contact the Project Manager: 
 
 
 
 
 
If only limited information is initially available, follow-up reports are required. Should the 
investigator become aware of an SAE (regardless of its relationship to test article) that 
occurs within 30 days after stopping the test article, the SAE must be reported in 


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accordance with procedures specified in this protocol. In the event of death, if an autopsy 
is performed, a copy of the report should be sent to TI, if available. 
 
Upon receiving such notices, the investigator must review and retain the notice with the 
Reference Product package insert and promptly submit a copy of this information to the 
responsible IRB according to local regulations. The investigator and IRB will determine if 
the informed consent/assent require revision. The investigator should also comply with the 
IRB procedures for reporting any other safety information. Where required, submission of 
safety updates by the investigator to Health Authorities should be handled according to 
local regulations. 
 
The Sponsor or designee may be required to report certain SAEs to regulatory authorities 
(e.g., United States FDA) within 7 calendar days of being notified about the event; 
therefore, it is important that investigators submit any information requested by the 
Sponsor or designee as soon as it becomes available. 
14.4 
Laboratory Test Abnormalities 
There are no specific laboratory tests, other than UPT, required in this study.  
14.5 
Pregnancy 
WOCBP (see Schedule of Events for definition of WOCBP) must have a UPT prior to 
study enrollment. Prior to study enrollment, WOCBP must be advised of the importance 
of avoiding pregnancy during the study and the potential risk factors for an unintentional 
pregnancy. The subject must sign an informed consent/assent (if applicable) form 
documenting this discussion. 
 
WOCBP should be instructed to contact the investigator immediately if they suspect they 
might be pregnant (e.g., missed or late menstrual period) during the study and for 30 days 
after she has completed her last test article application. If a subject or investigator suspects 
that a subject may be pregnant at any time during the study, the test article must be withheld 
until the results of laboratory pregnancy testing are available. If pregnancy is confirmed, 
the subject must not receive or apply further test article and the subject must be 
discontinued from the study. 
 
If following initiation of study treatment, it is subsequently discovered that a subject was 
pregnant or may have been pregnant at the time of test article exposure, the investigator 
must immediately notify the Medical Monitor of this event and record the pregnancy on 
the appropriate pregnancy surveillance form. The form will be sent to TI. The investigator 
will also report any pregnancy associated with the study treatment as required by their IRB 
and keep careful source documentation of the event. 
 
Protocol-required procedures for those subjects that are discontinued from the study must 
be performed on the subject unless contraindicated by pregnancy (e.g., x-ray studies). 


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Other appropriate pregnancy follow-up procedures should be considered if indicated, 
including counseling of the subject by the investigator and her managing physician or 
health care provider (e.g., obstetrician). In addition, the investigator must report to TI, on 
the appropriate pregnancy surveillance form(s), any follow-up information regarding the 
course of the pregnancy, including perinatal and neonatal outcome. Although pregnancy 
itself is not an AE, any complications during pregnancy should be recorded as AEs or SAEs 
(if they fulfill the SAE criteria). Offspring should be followed for a minimum of 8 weeks. 
Any congenital anomaly/birth defect in a child born to a subject exposed to the test 
article(s) should be recorded as an SAE with details documented in the pregnancy 
surveillance form. Abortion, whether accidental, therapeutic, or spontaneous should be 
reported as an SAE. Elective abortions are generally not reported as an SAE unless an AE 
occurs that meets the criteria for an SAE. 
15. 
BLINDING/UNBLINDING 
This is a double-blind, randomized, placebo-controlled study. Blinding is important for the 
integrity of this clinical study. Test article will be packaged in identical bottles so that 
neither the subject, investigator nor site staff will know the identity of the contents. 
However, the blind may be broken in the event of a medical emergency in a subject, in 
which knowledge of the test article identity is critical to the subject’s management. Before 
breaking the blind for a subject, the investigator should determine that the information is 
necessary (i.e., that it will alter the subject’s immediate management). In many cases, 
particularly when the emergency is clearly not test article related, the problem may be 
effectively managed by assuming that the subject is receiving active product without the 
need for unblinding. The need to break the blind should first be discussed with the 
responsible Medical Monitor if possible prior to breaking the blind and the best method to 
do this will be determined. 
 
A sealed copy of the randomization scheme should be retained at the study site and should 
be available to FDA investigators at the time of site inspection to allow for verification of 
the treatment identity of each subject. 
16. 
CLINICAL SUPPLIES 
16.1 
Test Article Information 
Detailed information on the packaging/labeling, blinding/unblinding, storage and 
preparation, dispensing, accountability, etc. of the test article is included in Appendix 3. 
16.2 
Supplies Provided by Therapeutics, Inc. 
 eCRFs 
 Source document draft templates 
 Site regulatory binder 
 UPT kits 


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 Weighing scales for test article  
 Digital camera 
16.3 
Supplies Provided by Investigator 
 Urine collection containers for UPTs 
16.4 
Supplies Provided by Gage Development Company, LLC 
 Test article 
 Samples for demonstration to subjects of test article application 
17. 
STATISTICAL CONSIDERATIONS 
17.1 
Sample Size 
Based on the assumption of a 40% reduction in inflammatory and non-inflammatory 
lesions counts for the Reference Product and a 38% reduction for GDC 268, 346 PP 
subjects per active arm will provide 85% probability of demonstrating therapeutic 
equivalence between the two active treatments at an alpha=0.05 (two one-sided tests) with 
90% confidence interval bounds of the ratio of means being 0.08 and 1.25. Assuming a 
25% reduction in inflammatory and non-inflammatory lesions counts for the VEH, 231 
mITT subjects in the VEH arm and 462 mITT subjects in each of the active treatment arms 
will provide at least an 85% probability of demonstrating that each active treatment is 
statistically superior to vehicle treatment at a two-sided alpha of 0.05. Therefore, 
approximately 1200 subjects will be enrolled using a 2:2:1 randomization ratio (GDC 268: 
Reference Product: VEH) to obtain a total of 1155 mITT subjects and 865 PP subjects.  
17.2 
Endpoints 
17.2.1 Efficacy Endpoints 
Co-primary efficacy endpoints will include: 
 
Percent change from Baseline to Week 12 in the inflammatory (papules and 
pustules) lesion count. 
 
Percent change from Baseline to Week 12 in the non-inflammatory (open and 
closed comedones) lesion count. 
17.2.2 Safety Endpoints 
Safety endpoints will include: 
 
Incidence (severity and causality) of any reported or observed treatment emergent 
AEs, whether or not they are considered to be related to the test article. 


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 
Number of subjects with improved/same versus worsened severities compared to 
Baseline 
of 
the 
following 
LSRs: 
erythema, 
edema, 
scaling/dryness, 
stinging/burning, pruritus, erosion, and pain at each onsite treatment visit. 
17.3 
Statistical Methods 
All statistical processing will be performed using SAS® Version 9.4 unless otherwise stated.  
 
The Safety population will include all randomized subjects who applied at least one dose of 
test article.  
 
The mITT population will include all randomized subjects who applied at least one dose of 
test article.  
 
The PP population will include all mITT subjects who met all I/E criteria, were compliant 
with the assigned test articles based on the subject diaries (applied at least 75% and no more 
than 125% of the expected test article applications for the specified duration of the study), 
did not miss the scheduled test article applications for more than 3 consecutive days (i.e., 3 
consecutive days with no test article application), have no other evidence of material dosing 
noncompliance, and completed the primary endpoint evaluation at Week 12 within the 
designated visit window (Day 85 ± 4 days) with no protocol violations that would affect the 
treatment evaluation including use of the prohibited medications. 
 
Subject randomization will be stratified by the number of non-inflammatory lesions (≤70 / 
>70) present at the Baseline Visit in order to ensure balanced enrollment of subjects across 
the treatment groups by non-inflammatory lesion count. No subset analyses are planned 
based on baseline non-inflammatory lesion counts. 
17.3.1 Dosing Compliance 
Descriptive statistics will be used to summarize test article compliance for each analysis 
population. Compliant subjects are defined as those who apply at least 75% and no more 
than 125% of the expected test article applications, and did not miss scheduled applications 
for more than 3 consecutive days. The percentage of compliant subjects will be also 
presented. 
17.3.2 Efficacy Analyses 
The efficacy analyses will be conducted on the mITT and PP populations.  
17.3.2.1 
Primary Efficacy Analyses 
For each of the co-primary endpoints (percent change from Baseline at Week 12 in the 
inflammatory lesion counts and in the non-inflammatory lesion counts), the 90% 
confidence interval of the ratio of the mean percent reduction in lesion counts between the 


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GDC 268 group and the Reference Product group will be assessed in the PP population. If 
the 90% confidence intervals are contained within the interval [0.8, 1.25] for both 
inflammatory and non-inflammatory lesions, bioequivalence between GDC 268 and the 
Reference Product will be demonstrated. 
 
The percent change from Baseline at Week 12 in the inflammatory lesion counts and in the 
non-inflammatory lesion counts for each GDC 268 and Reference Product group will be 
compared against VEH group at an alpha=0.05 (p<0.05) in the mITT population using last 
observation carried forward (LOCF) imputation using analysis of variance (ANOVA) with 
factor of treatment in the statistical model using original percent change values. 
 
If the distribution of percent change from Baseline in the lesion counts are significantly 
skewed, the analyses will be performed based on rank transformed data. 
17.3.2.2 
Exploratory Efficacy Analysis 
The frequency distribution of the observed and change from Baseline IGA scores will be 
presented at each visit by treatment group for the mITT and PP populations. 
17.3.2.3 
Imputation of Missing Data 
Subjects who are discontinued early from the study due to lack of treatment effect after 4 
weeks of treatment will be included in the PP population analyses using LOCF. Subjects 
whose condition worsens and who require alternate or supplemental therapy for the 
treatment of their condition during the treatment phase of the study will be included in the 
mITT and PP population analyses using LOCF. Subjects discontinued early for other 
reasons will be excluded from the PP population, but included in the mITT population, 
using LOCF. 
17.3.2.4 
Sensitivity Analysis 
No sensitivity analyses are planned. Any additional analyses performed will be described 
in the final clinical study report. 
17.3.2.5 
Multiple Comparisons / Multiplicity 
Not applicable. 
17.3.3 Safety Analyses 
All safety analyses will be performed in the Safety population unless otherwise stated. 
17.3.3.1 
Adverse Events 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
coding dictionary. The number and percent of unique subjects reporting each treatment-


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emergent AE will be summarized by MedDRA system organ class (SOC), MedDRA 
preferred term (PT), and treatment group. AEs will also be similarly summarized by SOC, 
PT, maximum severity, and treatment group as well as by SOC, PT, closest relationship to 
test article, and treatment group. All AEs reported during the study will be listed. 
17.3.3.2 
Local Skin Reactions 
The frequency of the individual LSRs (erythema, edema, scaling/dryness, stinging/burning, 
pruritus, erosion, and pain) will be tabulated by severity and treatment group at each onsite 
clinic visit. Subject counts for improved/same versus worsened compared to Baseline value 
will be also presented for the post-baseline visits. 
17.4 
Subgroup Analyses 
No subgroup analyses are planned. 
17.5 
Interim Analyses 
No interim analyses are planned. 
18. 
ETHICAL AND REGULATORY CONSIDERATIONS 
18.1 
Compliance with Good Clinical Practice 
This study will be conducted in compliance with the principles of the Declaration of 
Helsinki, with the current Good Clinical Practice guidelines and with other applicable 
regulations. The investigator and all study staff will conduct the study in compliance with 
this protocol. The protocol, informed consent/assent (if applicable) documents, recruitment 
advertisements, and any amendments to these items will have IRB approval, where 
required, prior to study initiation. Voluntary informed consent/assent (if applicable) will 
be given by every subject prior to the initiation of any study-related procedures. The rights, 
safety and well-being of the study subjects are the most important considerations and 
prevail over the interests of science and society. All personnel involved in the conduct of 
this study must be qualified by education, training, and experience to perform their 
assigned responsibilities. Contact information for each site and any clinical laboratories 
used in the study will be maintained up to date in a separate reference document. 
18.2 
Institutional Review Board and Informed Consent 
Before study initiation, the investigator must have written and dated approval from the IRB 
for the protocol, consent/assent form, subject recruitment materials/process (e.g., 
advertisements), and any other written information to be provided to the subject/and 
parent/guardian (if applicable). The investigator should also provide the IRB with a copy 
of the product labeling, information to be provided to the subject/and parent/guardian (if 
applicable) and any updates. The investigator will submit documentation of the IRB 
approval to TI.  


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The IRB-approved consent/assent form must include all elements required by FDA, state, 
and local regulations, and may include appropriate additional elements. 
 
The investigator/qualified designee will explain the study to each potential subject and 
parent/guardian (if applicable) and the subject must indicate voluntary consent/assent by 
signing and dating the approved informed consent/assent (if applicable) form. The parent 
or legal guardian must provide written informed consent for the subject. The investigator 
must provide the subject and parent/guardian (if applicable) with a copy of the 
consent/assent (if applicable) form, in a language the subject understands.  
 
The investigator will maintain documentation that informed consent was obtained prior to 
the initiation of any study-specific procedures. 
18.3 
Protocol Compliance 
The IRB-approved protocol must be followed except in the case of a change that is intended 
to eliminate an immediate risk to subjects. All protocol deviations must be documented.  
18.4 
Protocol Revisions 
The Sponsor or designee must prepare all protocol revisions. All protocol amendments 
must receive IRB approval prior to implementation. All administrative letters must be 
submitted to the IRB for their information. Copies of all correspondence with the IRB 
regarding this study must be sent to TI. 
 
New or altered consent/assent forms required by the IRB due to a protocol change must be 
signed by all subjects and parent/guardians (if applicable) currently enrolled in the study 
and must be used for any subsequent subject enrollment. 
18.5 
Study Monitoring 
Representatives of TI and/or the Sponsor must be allowed to visit all study sites, to review 
study records, and to directly compare them with source documents (including, but not 
limited to patient and hospital records, the source document worksheet, and any electronic 
medical records (i.e., access to EMRs in a HIPAA compliant manner or if that is not 
possible certified copies must be available from the EMR system with 10% over the 
shoulder review), to discuss the study conduct with the investigator and study staff, and to 
verify that the investigator, study staff, and facilities remain acceptable for the conduct of 
the study. 
 
Representatives of government regulatory authorities may also evaluate the study records, 
source documents, investigator, study staff, and facilities. 
 


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The investigator should immediately notify TI of any audits of this study by any regulatory 
agency and must promptly provide copies of any audit reports. 
18.6 
Case Report Form Requirements 
The study will utilize eCRFs. Validated 21 CFR Part 11 compliant electronic data capture 
(EDC) software will be used to collect data. All requested information must be entered on 
the eCRFs in the areas provided in a timely manner. When changes or corrections are made 
in the eCRF, the EDC system will maintain a complete audit trail of the person making the 
changes, the date and time of the change, and the reason for the change. Only individuals 
who have completed EDC training and are listed on the Delegation of Responsibilities Log 
with responsibility for eCRF completion will be provided usernames and passwords in 
order to access the system and make entries on the eCRF. 
 
The investigator or physician sub-investigator must electronically sign and date each 
subject’s eCRF. Individuals who will be providing electronic signatures must first submit 
documentation with a handwritten signature acknowledging that their electronic signature 
is a legally binding equivalent to their handwritten signature. 
18.7 
Reports to Institutional Review Board 
The investigator should provide the IRB with reports, updates, and other information (e.g., 
safety updates, protocol amendments, and administrative letters) according to regulatory 
requirements or Institution procedures. 
18.8 
Quality Assurance Audits 
Representatives from TI and/or the Sponsor or a third party selected by the Sponsor may 
conduct a quality assurance audit of this study. During the audit, the investigator must 
provide the auditor with direct access to all relevant documents and discuss any findings 
with the auditor. 
 
In the event of an inspection by the FDA or other regulatory authorities, the investigator 
must give the inspector direct access to relevant documents and to discuss any findings 
with the inspector. The investigator must notify TI in the event of a FDA site audit. 
18.9 
Records Retention 
According to 21CFR § 312.62, an investigator is required to maintain study records for a 
period of 2 years following the date a marketing application is approved for the test article 
for the indication for which it is being investigated; or, if no application is to be filed or if 
the application is not approved for such indication, until 2 years after the investigation is 
discontinued and the FDA is notified. 
 


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Each site will be required to randomly select reserve samples from the shipment of test 
articles. Instructions on the number of kits to select and how to document the kit numbers 
selected as reserve samples will be included in the shipment. Each site will then store the 
reserve samples. In accordance with 21CFR § 320.38, each reserve sample (retain) shall 
be stored under conditions consistent with product labeling and in an area segregated from 
the area where testing is conducted and with access limited to authorized personnel. Each 
reserve sample shall be retained for a period of at least 5 years following the date on which 
the application or supplemental application is approved, or, if such application or 
supplemental application is not approved, at least 5 years following the date of completion 
of the bioavailability study from which the reserve sample was obtained. 
 
The investigator must contact TI or the Sponsor in writing to obtain consent prior to 
destroying any records or reserve samples associated with this study. 
 
If the investigator withdraws from the study, the records shall be transferred to a mutually 
agreed upon designee. Written notification of such a transfer must be given to TI. 
18.10 Record Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in 
a manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the 
written permission of the subject or the subject’s parent/guardian (if appropriate), except 
as necessary for monitoring by TI or the Sponsor, the FDA or other regulatory authority, 
or the IRB. 
 
The investigator and all employees and coworkers involved with this study shall not 
disclose or use for any purpose other than performance of the study, any data, records, or 
other unpublished, confidential information disclosed to those individuals for the purpose 
of the study. Prior written agreement from TI or the Sponsor must be obtained for the 
disclosure of any said confidential information to other parties. 
 
 


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19. 
REFERENCES 
1. 
White GM. Recent findings in the epidemiologic evidence, classification, and 
subtypes of acne vulgaris. Journal of the American Academy of Dermatology. 
1998;39:S34-7. 
2. 
Bhate K, Williams HC. Epidemiology of acne vulgaris. The British journal of 
dermatology. 2013;168:474-85. 
3. 
Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. 
Guidelines of care for the management of acne vulgaris. Journal of the American Academy 
of Dermatology. 2016;74:945-73.e33. 
4. 
FDA. Draft Guidance on Clindamycin Phosphate. Recommended Apr 2011; 
Revised Nov 2018. 
 
 


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APPENDIX 1 
SAMPLE SUBJECT INSTRUCTION SHEET 
Copies of the following sample subject instructions will be provided to the study site. The 
investigator must give each subject/parent/guardian (if applicable) a copy of this instruction 
sheet at Visit 1/Baseline. 
 
 
 




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TI 305-A Protocol Template, Version 07 
 
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Template Effective Date: 31 OCT 2016 
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APPENDIX 2 
SAMPLE SUBJECT DIARY 
A copy of the following sample Subject Diary will be provided to the study site. The 
investigator must give each subject/parent/guardian (if applicable) a copy of this Subject 
Diary at Visit 1/Baseline and all follow-up visits, as necessary. 
 
 


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SAMPLE SUBJECT DIARY 


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APPENDIX 3 
TEST ARTICLE INFORMATION 


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APPENDIX 4 
PROTOCOL AMENDMENTS 


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CONTROLLED & CONFIDENTIAL 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
Page 65 of 66 
 
CONTROLLED & CONFIDENTIAL 


Product Name: GDC 268 
 
Protocol: GDC-268-001 
Sponsor Name: Gage Development Company, LLC Protocol Date: September 6, 2019, v3.0 
 
Page 66 of 66 
 
CONTROLLED & CONFIDENTIAL