The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612000062820
Ethics application status
Approved
Date submitted
12/12/2011
Date registered
12/01/2012
Date last updated
10/08/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Isotretinoin 5mg capsules (once daily) in the treatment of persistent low grade adult acne.
Scientific title
Randomized, double-blind, placebo-controlled, parallel group clinical study of Isotretinoin 5 mg capsules (once daily) in the treatment of persistent low grade adult acne for 16 weeks followed by an open-label phase of 16 weeks - Protocol Number: ZPS-365
Secondary ID [1] 273502 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent low grade adult acne. 279296 0
Condition category
Condition code
Skin 279492 279492 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients are randomised to receive orally one Isotretinoin 5 mg capsule daily for 32 weeks or placebo for 16 weeks followed by one Isotretinoin 5 mg capsule daily for 16 weeks. A 10 week follow-up period for all patients occurs at the completion of the treatment phase.
Intervention code [1] 283819 0
Treatment: Drugs
Comparator / control treatment
Placebo soft gel capsules developed to be indistinguishable in smell, taste and appearance but without the active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 286056 0
To assess the efficacy of isotretinoin 5mg daily compared to placebo in persistent low grade adult acne. The Investigator will perform a clinical assessment of the acne lesion count at week 16, adjusted for the acne lesion count at day 0.
Timepoint [1] 286056 0
Over 16 weeks
Secondary outcome [1] 295054 0
The Investigator will perform a clinical assessment of the acne lesion count at weeks 32 and 42 between Groups 1 and 2 and within Group 2 at Weeks 16 and 32.
Timepoint [1] 295054 0
At weeks 16, 32 and 42 after intervention commencement, as per above outline.
Secondary outcome [2] 295055 0
To assess the erythema severity score between Groups 1 and 2 at Weeks 16, 32 and 42; and within Group 2 at Weeks 16 and 32.
Timepoint [2] 295055 0
At weeks 16, 32 and 42 after intervention commencement, as per above outline.
Secondary outcome [3] 295056 0
To assess changes in Quality of Life (questionnaire and self assessment of acne) between treatment Groups 1 and 2 at Weeks 16, 32 and 42, and for group 2 between week 16 and 32 timepoints.
Timepoint [3] 295056 0
At weeks 16, 32 and 42 after intervention commencement, as per above outline.
Secondary outcome [4] 295057 0
To assess the safety of isotretinoin 5mg daily at the end of each period (Weeks 16, 32 and 42). The Investigator will ask the participant if they have experienced any adverse events and review the participants diary card at each visit to ascertain if any adverse events have occurred.
Timepoint [4] 295057 0
At weeks 16, 32 and 42 after intervention commencement, as per above outline.

Eligibility
Key inclusion criteria
Male or female aged between 25 and 55 years at the time of randomization.

If the participant is female, she should be either: post menopausal for at least 1 year, surgically sterile for at least 3 months, stable on hormonal contraceptives for at least 6 months and agree to continue these during the study and for 30 days after treatment completion, or be willing to use double-barrier contraception for the duration of the study and for 30 days after treatment completion.

Two or more acne lesions/month for at least the last 3 months as reported by the participant and evident at the time of consultation.

BMI between 19 and 35.

Provide signed and dated written informed consent.

Be willing and able to comply with the requirements of the study including taking study medication as directed.
Minimum age
25 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Less than two acne lesions /month.

Acne of Grade 2 or more on the Modified Leeds Acne Assessment Scale.

Participants with 10 or more macro comedones.

Concomitant drug therapy with Vitamin A or its derivatives, tetracyclines, keratolytic or exfoliative antiacne treatments, carbamazepine, spironolactone, azelaic acid, St. Johns Wort or preparations containing St. Johns Wort.

Participants who have received any antibiotic treatment within the 3 months preceding the start of the study.

Participants who have used topical retinoids in the month preceding the start of the study (participants using cosmetics that include low dose topical retinoids will not be excluded).

Females receiving estrogen and/or progesterone treatment, unless on a stable dose for at least 6 months preceding the start of the study and still with persistent acne. If females are using Mirena it must have been in place for at least 6 months preceding the start of the study.

Participants receiving glucocorticoid treatment within one month preceding the start of the study (except for inhaled corticosteroids for asthma where the dose should be stable throughout the study and not exceed 1 mg/day).

Participants who have received treatment with isotretinoin within 6 months of the commencement of the study.

Participants with a known or reported history of Hypervitaminosis A, depression, psychoses, cardiovascular disease, renal disease, lipid disorders, epilepsy, glaucoma, cataract, hepatic disease, diabetes, pancreatitis, blood disorders including anaemia, recurrent migraine headaches, dry eye syndrome or any other condition in the opinion of the investigator that would compromise the safety of the participant or confound the study endpoints. Any participant with a serious or unstable concurrent disease will be excluded from the study.

Participants who are found to have elevated triglyceride levels or abnormal liver function assessed as clinically significant by the Investigator at the screening blood test.

Participants with a history of alcohol abuse or drug addiction.

Participants who are known to be Hepatitis A, B or C or HIV positive at the time of screening.

Participants who have participated in another drug study in the 60 days preceding the start of the study.

Participants who are sensitive to isotretinoin and other vitamin A derivatives or are severely allergic to other substances.

Female participants who are pregnant or who are planning to become pregnant during the course of the study. Female participants must agree to adhere to the study requirement in relation to contraception.

Females who are breastfeeding.

Participants who do not agree to NOT donate blood for two months after the completion of the study.

Participants, who do not, according to the Investigator, understand the information and procedures of the study, in particular the study restrictions and risks involved.

Participants who are unable to conform to the requirements of the protocol.

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)
Each investigational site is allocated a unique site number and medication packs with designated randomisation numbers. At each site, participants will be sequentially allocated a randomisation number after they meet the entry criteria and issued with the corresponding medication pack. The code break for the randomised medication packs are held in sealed envelopes at the Lead Clinical site and at the Sponsor's premises, and will only be opened in the event of an emergency. Until a code-break occurs the investigators, clinicians and the subjects are unaware which medication (placebo or isotretinoin) has been allocated.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation list computer generated.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 3986 0
New Zealand
State/province [1] 3986 0

Funding & Sponsors
Funding source category [1] 284289 0
Commercial sector/Industry
Name [1] 284289 0
Douglas Pharmaceuticals Ltd
Address [1] 284289 0
Cnr Te Pai Place and Central Park Drive,
Lincoln,
Auckland 0610
Country [1] 284289 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Douglas Pharmaceuticals Ltd
Address
Cnr Te Pai Place and Central Park Drive,
Lincoln,
Auckland 0610
Country
New Zealand
Secondary sponsor category [1] 283241 0
None
Name [1] 283241 0
Address [1] 283241 0
Country [1] 283241 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286254 0
Northern Y Regional Ethics Committee
Ethics committee address [1] 286254 0
Ministry of Health,
3rd Floor, BNZ Building,
354 Victoria Street,
PO Box 1031,
Hamilton
Ethics committee country [1] 286254 0
New Zealand
Date submitted for ethics approval [1] 286254 0
Approval date [1] 286254 0
23/07/2007
Ethics approval number [1] 286254 0
NTY/07/05/044

Summary
Brief summary
Isotretinoin is a retinoid, structurally related to vitamin A, which has been used orally in human medicine for more than 20 years in the treatment of severe acne resistant to other treatments. A large body of published data, from both human and animal studies, suggests that the clinically useful action of isotretinoin is to reduce both the size and secretory capacity of sebaceous glands. Although isotretinoin has no significant in vitro antibacterial activity, when used orally to treat acne it causes a significant reduction in the numbers of skin bacteria. This effect is generally believed to be secondary to its action in reducing sebum production and may contribute to its useful action in treating acne.

Some recent publications suggest lower doses of isotretinoin may be a useful alternative for patients who present with less severe acne. The clinical efficacy of treating specific patient groups with a daily low dose alternative to complicated periodic or interrupted dose schedules with higher strength capsules needs further investigation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33466 0
Dr Marius Rademaker
Address 33466 0
Tristram Clinic
6 Knox Street
Hamilton
3204
Country 33466 0
New Zealand
Phone 33466 0
+64 7 838 1035
Fax 33466 0
Email 33466 0
rademaker@xtra.co.nz
Contact person for public queries
Name 16713 0
Mrs Samantha Marsh-Patrick
Address 16713 0
Douglas Pharmaceuticals Limited
P.O.Box 45 027,
Te Atatu Peninsula,
Auckland 0651
Country 16713 0
New Zealand
Phone 16713 0
+ 64 9 8350660
Fax 16713 0
+ 64 9 8350690
Email 16713 0
samantham@douglas.co.nz
Contact person for scientific queries
Name 7641 0
Dr Dr Marius Rademaker
Address 7641 0
Tristram Clinic
6 Knox St
Hamilton
3204
Country 7641 0
New Zealand
Phone 7641 0
+64 7 8381035
Fax 7641 0
+64 7 8382032
Email 7641 0
rademaker@xtra.co.nz

No information has been provided regarding IPD availability
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