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Trial registered on ANZCTR


Registration number
ACTRN12619000406101
Ethics application status
Approved
Date submitted
8/03/2019
Date registered
13/03/2019
Date last updated
8/02/2021
Date data sharing statement initially provided
13/03/2019
Date results information initially provided
8/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment of Melasma with Cysteamine cream compared to Hydroquinone cream
Scientific title
Evaluation of the efficacy of cysteamine cream compared to hydroquinone cream in the treatment of melasma: a randomised, double-blind, multi-centre trial.
Secondary ID [1] 297657 0
Nil known
Universal Trial Number (UTN)
U1111-1229-7027
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melasma 311933 0
Condition category
Condition code
Skin 310517 310517 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised in a 1:1 ratio to apply either Cysteamine cream or Hydroquinone cream.

Arm 1 (intervention) - Participants to apply a thin layer of Cysteamine 5% cream in the evening to the affected areas of a clean face (washed with water or a gentle cleanser). After 15 minutes, the cream should be washed off, and the placebo cream applied to the affected areas and left on overnight. The Cysteamine tube is labelled 'apply first' and the placebo tube is labelled 'apply second' to maintain the double-blind nature of the trial.

Compliance will be assessed by questioning the participant at week 2 and 4 phone calls and at study visits week 8 and 16. It is likely that a single 50g tube will last the participant 16 weeks, however if participants need an additional tube of study drug they will need to return the empty study drug tube to receive a second tube.

Participants will be instructed to apply a standardised broad spectrum SPF 50+ sunscreen evenly and generously to the face 20 minutes prior to sun exposure. It is water resistant for 40 minutes and should be reapplied immediately after 40 minutes of swimming or sweating, otherwise reapplied 2-hourly during sun-exposure.
Intervention code [1] 313890 0
Treatment: Drugs
Comparator / control treatment
Arm 2 (intervention) - Participants to apply a thin layer of placebo cream in the evening to the affected areas of a clean face (washed with water or a gentle cleanser). After 15 minutes, the cream should be washed off, and the Hydroquinone 4% cream in a stabilised emollient ascorbic acid base applied to the affected areas and left on overnight. The placebo tube is labelled 'apply first' and the Hydroquinone tube is labelled 'apply second' to maintain the double-blind nature of the trial.

Participants will be instructed to apply a standardised broad spectrum SPF 50+ sunscreen evenly and generously to the face 20 minutes prior to sun exposure. It is water resistant for 40 minutes and should be reapplied immediately after 40 minutes of swimming or sweating, otherwise reapplied 2-hourly during sun-exposure.
Control group
Active

Outcomes
Primary outcome [1] 319373 0
Efficacy: Change from baseline in Modified Melasma Area Severity Index (mMASI) score at week 16 in Arm 1 compared to Arm 2.
Timepoint [1] 319373 0
Baseline (week 0), week 8, week 16 (primary timepoint)
Primary outcome [2] 319374 0
Safety: Number of adverse effects in the Cysteamine group compared to the Hydroquinone group.

The type and nature of any adverse effects will be recorded in a study specific questionnaire at week 2 and 4 phone calls, and at weeks 8 and 16 study visits.

The questionnaire assesses presence of common adverse events (irritation, dryness, redness, scaliness, itching, burning, worsening of pigmentation, rashes) as well as the severity of any reported adverse events (mild, moderate or severe and rated on a scale of 0-10).

In addition, an examination of the face will be conducted by a researcher at weeks 8 and 16 study visits to assess for any possible adverse events.
Timepoint [2] 319374 0
Baseline, week 2, week 4, week 8, week 16 (primary timepoint)
Secondary outcome [1] 367922 0
A secondary outcome of the study is the proportion of participants improving according to change from baseline modified Melasma Area Severity Index (mMASI) and change in quality of life (QOL) as assessed by the standardised Melasma QOL questionnaire.
Timepoint [1] 367922 0
Week 8, Week 16
Secondary outcome [2] 367923 0
A standardised melasma quality of life questionnaire (MelasQOL)
Timepoint [2] 367923 0
Week 0, Week 8, Week 16

Eligibility
Key inclusion criteria
1. Must provide informed consent
2. Must be over the age of 18 and female
3. Moderate to severe melasma defined by the following at screening visit:
a. Modified MASI scoring
4. Melasma present for at least 3 months
5. Willing and able to comply with study instructions and return to the study site for required visits
6. Must be able to comply with the study regimen for the duration of the study.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant or breastfeeding
2. Rashes on the face
3. Job which is primarily outdoors (more than 2 hours per day) or goes to tanning salons
4. Hydroquinone, or other bleaching agents, used within the last month
5. Topical steroid applied to the face within the last month
6. Retin A, retinol, tretinoin, Differin, or adapalene used within the last month
7. Laser treatment to the face within the last month

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
• We expect a 30-40% change in MASI in the hydroquinone group and 60-80% change in MASI in the cysteamine group.
• Hq = hydroquinone group where participants are treated with hydroquinone and sunscreen.
• Cy = cysteamine and sunscreen treatment group.
• Using the expected proportional change of 60% for Cy (48.5 to 19.4=29.1) and expected proportional change 30% for Hq (48.5 to 33.96 = 14.56) results in a mean difference of 14.54 and a standard deviation (SD) of 8.21.
• Using R with the power package to determine the sample size, a power of 80%, a two-sided level of significance of 5% and equal groups sizes for the calculation results in a total number of 40 participants in each group. The sample size was adjusted for t-distribution for Comparing Two Independent Means.
• Assuming the MASI results to be continuous and normally distributed, a simple paired sample t-test will suffice for the primary endpoint of calculating the significance of difference between MASI scores when cysteamine is applied compared to hydroquinone. Otherwise, an ANOVA test would be suitable.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
This study was planned as a multi-centre trial. However due to logistical difficulties at other sites, only one centre recruited patients.
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13343 0
Chroma Dermatology - Wheelers Hill
Recruitment postcode(s) [1] 25930 0
3150 - Wheelers Hill
Recruitment outside Australia
Country [1] 21335 0
Netherlands
State/province [1] 21335 0
Amsterdam
Country [2] 21336 0
Singapore
State/province [2] 21336 0
Singapore

Funding & Sponsors
Funding source category [1] 302188 0
Commercial sector/Industry
Name [1] 302188 0
Scientis Pharma SA
Address [1] 302188 0
Avenue de Sécheron 15, 1202 Genève, Switzerland
Country [1] 302188 0
Switzerland
Primary sponsor type
Individual
Name
Dr Michelle Rodrigues
Address
Chroma Dermatology
G15/202 Jells Rd
Wheelers Hill
3150 VIC
Country
Australia
Secondary sponsor category [1] 302030 0
None
Name [1] 302030 0
Address [1] 302030 0
Country [1] 302030 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302868 0
Bellberry Ltd
Ethics committee address [1] 302868 0
123 Glen Osmond Road, Eastwood, Adelaide
South Australia 5063
Ethics committee country [1] 302868 0
Australia
Date submitted for ethics approval [1] 302868 0
26/11/2018
Approval date [1] 302868 0
24/04/2019
Ethics approval number [1] 302868 0

Summary
Brief summary
Melasma is a common disorder of hyperpigmentation, manifesting as slowly-expanding tan-brown macules, primarily affecting the face.

This study is a randomised, double-blind efficacy study of cysteamine cream compared to hydroquinone cream. Participants will be asked to come for study visits at weeks 0, 8, and 16. At weeks 2 and 4, participants will receive a phone call to assess for any adverse side effects.

At the baseline visit, each participant will be randomised into one of two arms. Participants will apply the drug to which they have been randomised daily and use a supplied sunscreen to the entire face during the day.

Efficacy of the treatments will be measured by clinical examination of the face including modified Melasma Area Severity Index, digital photographs and the MelasQOL (quality of life) questionnaire. Adverse events will be monitored at each study visit and phone call.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91666 0
Dr Michelle Rodrigues
Address 91666 0
Chroma Dermatology, G15/202 Jells Rd, Wheelers Hill, 3150, VIC
Country 91666 0
Australia
Phone 91666 0
+61 03 8560 6946
Fax 91666 0
Email 91666 0
info@chromaderm.com.au
Contact person for public queries
Name 91667 0
Dr Jennifer Nguyen.
Address 91667 0
Chroma Dermatology, G15/202 Jells Rd, Wheelers Hill, 3150, VIC
Country 91667 0
Australia
Phone 91667 0
+61 03 8560 6946
Fax 91667 0
Email 91667 0
info@chromaderm.com.au
Contact person for scientific queries
Name 91668 0
Dr Michelle Rodrigues
Address 91668 0
Chroma Dermatology, G15/202 Jells Rd, Wheelers Hill, 3150, VIC
Country 91668 0
Australia
Phone 91668 0
+61 03 8560 6946
Fax 91668 0
Email 91668 0
info@chromaderm.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data underlying published results only.
When will data be available (start and end dates)?
Data will be available immediately following publication for 10 years.
Available to whom?
Case-by-case basis at the discretion of the Primary Sponsor.
Available for what types of analyses?
To achieve the aims in the proposed protocol.
How or where can data be obtained?
Access subject to approval by Primary Investigator.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary