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Trial registered on ANZCTR


Registration number
ACTRN12613001226796
Ethics application status
Approved
Date submitted
5/11/2013
Date registered
7/11/2013
Date last updated
29/06/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Anti-inflammatory treatment for dermatological disorders.
Scientific title
A Phase I, randomised, double blind, placebo-controlled, study of the safety, tolerability, pharmacokinetics and clinical activity of AKP-11 administration to healthy volunteers and patients with mild to moderate psoriasis.
Secondary ID [1] 283542 0
NA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Inflammatory skin diseases 290433 0
Psoriasis 290451 0
Condition category
Condition code
Skin 290824 290824 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
AKP-11 is a small molecule entity with anti-inflammatory activity. The test item will be administered via topical as a 3% formulation to the healthy volunteers (single dose) and the subjects with the mild to moderate psoriasis (multiple dose, once a day for up to 28 days). The drug will be administered at clinical unit's site. The 16 subjects will receive the active.
Intervention code [1] 288219 0
Treatment: Drugs
Comparator / control treatment
Placebo will be tretaed with the blank cream excluding the active drug.
Control group
Placebo

Outcomes
Primary outcome [1] 290819 0
Part A: The determination of the safety and tolerability of AKP-11 administration to healthy volunteers. The evaluation will include brief physical examination, vital signs, triplicate 12-lead ECGs, blood and urine samples for clinical laboratory testing, blood samples for pharmacokinetic (PK) and pharmacodynamic (PD) assessments, review of concomitant medications and adverse events (AE) before and after drug administration.
Timepoint [1] 290819 0
Timepoints: Day -1, 1, 2, 3 and 7.
Primary outcome [2] 290840 0
Part B: The determination of the safety, tolerability and efficacy of AKP-11 when administered to patients with mild to moderate psoriasis. The safety and tolerability will be done as in Part A. Clinical efficacy will be assessed using the LPSI assessment system and plaque size assessment of the treated plaque. The Exit Evaluation will be conducted on Day 35, 7 days after the last dose of Investigational Product. Blood and urine samples will be collected for clinical laboratory assessments.
Timepoint [2] 290840 0
Timepoints: Baseline, Day 1, 7, 14, 21, 28 and 35.
Secondary outcome [1] 305361 0
Secondary Outcome 1: The determination of the pharmacokinetic profile (T1/2, AUC, Cmax etc) of AKP-11 in healthy volunteers. Timepoints: Day 1 and 2.
Timepoint [1] 305361 0
Timepoints: Day 1 and 2.
Secondary outcome [2] 305414 0
Secondary Outcome 2: The determination of the pharmacokinetic profile (T1/2, AUC, Cmax etc) of multiple doses of AKP-11 in patients with mild to moderate psoriasis. Timepoints: Baseline, Day 1, 7, 14, 21 and 28.

Timepoint [2] 305414 0
Timepoints: Baseline, Day 1, 7, 14, 21 and 28.

Secondary outcome [3] 305415 0
Secondary Outcome 3: The determination of the pharmacodynamic profile (blood cell count) of AKP-11 in patients with mild to moderate psoriasis. Timepoints: Baseline, Day 1, 3, 7, 14, 21, 28 and 35.
Timepoint [3] 305415 0
Timepoints: Baseline, Day 1, 3, 7, 14, 21, 28 and 35.
Secondary outcome [4] 305416 0
Secondary Outcome 4: The determination of the efficacy profile, by the PsO Clinical Assessment (Thickness, Scaling, Erythema) of multiple doses of AKP-11 in patients with mild to moderate psoriasis. Timepoints: Baseline, Day 1, 7, 14, 21, 28 and 35.
Timepoint [4] 305416 0
Timepoints: Baseline, Day 1, 7, 14, 21, 28 and 35.

Eligibility
Key inclusion criteria
1. Males or females healthy or psoriasis patients aged from 18 upto 65 years at the time of screening.
2. Patients with mild to moderate chronic plaque-type psoriasis with a PASI score greater than 5 and less than 10 (based on diagnosis by a suitably qualified Investigator).
3. For psoriasis patients the duration of psoriasis of at least one year with stable disease in both extent and severity for at least two weeks prior to the commencement of study treatment.
4. Able to provide written informed consent prior to the performance of any study specific procedures.
5. Subjects with a BMI between 18.0 and 35.0 kg/m2.
6. Female subjects of non-childbearing potential, defined as (1) having a documented tubal ligation at least 6 weeks prior to dosing; (2) having had a surgical bilateral oophorectomy (with or without hysterectomy); (3) at least 12 months of spontaneous amenorrhoea with follicle stimulating hormone (FSH) greater than 40 MIU/ml.
7. Female subjects of child-bearing potential with negative serum pregnancy test at screening and negative urine pregnancy test at check-in (Day -1), AND; Agrees to abstinence for the duration of the study and until 4 weeks after dosing with study drug; OR agrees to use condoms plus one other acceptable form of contraception; ie. intra-uterine device, hormonal contraception or a female diaphragm, from screening until 4 weeks after dosing with study drug; OR has only same-sex partners, when this is her preferred and usual lifestyle.
8. Male subjects with female partners of child-bearing potential must agree abstinence or to use condoms plus partner use of an acceptable contraceptive (intrauterine device, hormonal contraception or male condom plus female diaphragm) for the duration of the study and until 4 weeks after dosing with study drug.
9. Negative Human Immunodeficiency Virus (HIV), Hepatitis B and Hepatitis C Screening test results.
10. Subjects who are willing and able to comply with all study assessments and adhere to the protocol schedule.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Subjects with erythrodermic, guttate, palmar, plantar or generalised pustular forms of psoriasis or subjects with scalp, palmar or plantar psoriasis only.
2. Subjects with any skin condition other than psoriasis, in particular eczema, cutaneous infections, significant sun damage or an inherited skin disorder (other than psoriasis).
3. History of allergy and/ or hypersensitivity to any of the stated ingredients of the formulations.
4. A history of moderate to severe asthma during the last 10 years.
5. Major chronic inflammatory disease e.g rheumatoid arthritis, Crohn’s disease, SLE.
6. Congenital or acquired immunodeficiency or cancer prone syndrome.
7. History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation, or a history of Hepatitis B, Hepatitis C or HIV infection.
8. Subjects who have smoked more than 10 cigarettes a day in the last 12 months
9. History of malignancy (other than adequately treated skin carcinoma or carcinoma-in-situ of the cervix).
10. Treatment with any of the following within 4 weeks prior to the commencement of study treatment and for the duration of the study: systemic retinoids; immunosuppressant agents (e.g. methotrexate, cyclosporine, azathioprine, thioguanine prednisone, prednisolone, hydroxyurea or mycophenolate mofetil); phototherapy or photochemotherapy; high potency topical corticosteroids; “alternative medicine” treatments for psoriasis; or prolonged sun exposure or tanning bed use, which may in the opinion of the Investigator, modify disease activity.
11. Topical treatment within 2 weeks prior to commencement of study treatment and for the duration of the study, including: moderate potency topical corticosteroids; vitamin D analogues and topical retinoids; or keratolytics, coal tar and dithranol.
12. Have received any investigational research agent or therapeutic biologic within 30 days or 5 half-lives (whichever is longer) prior to the first dose of Investigational Product.
13. Have received an investigational vaccine within 6 months, a live attenuated vaccine within 60 days or a registered vaccine within 30 days prior to the first dose of the Investigational Product.
14. Use of any of the following prescription drugs: beta-blockers, diltiazem, verapamil, anti-arrhythmic drugs. Other prescription drugs may be allowed at the discretion of the Principal Investigator.
15. Any clinically significant history or presence of neurological, endocrinal, cardiovascular, pulmonary, hematological, malignant, immunologic, psychiatric, metabolic or other uncontrolled systemic disease, with the exclusion of psoriasis.
16. Have a bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
17. Have a psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within five years prior to enrolment, a history of suicide plan.
18. Any clinically significant abnormality at Screening determined by medical history, physical examination, blood chemistry, haematology, urinalysis and a 12-lead ECG.
19. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and baseline.
20. Any other condition which in the view of the Investigator is likely to interfere with the study or put the subject at risk.
21. Have clinical signs of active infection and/or a temperature of greater than 38.0°C at the time of screening. Study entry may be deferred at the discretion of the Principal Investigator.
22. Have evidence of alcohol abuse within 6 months prior to screening visit (i.e., more than fourteen units of alcohol per week [1 Unit equal to 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
23. Be unable to provide a pre-injection blood sample without undue trauma or distress.
24. Anticipate surgery within the trial period or history of major surgery within 3 months of screening.
25. History of hypersensitivity to the class of compound under investigation.
26. Use of over-the-counter products (including natural food supplements, vitamins, garlic as a supplement) within 7 days prior to administration of study treatment, except for topical products without systemic absorption.
27. A depot injection or an implant of any drug within 3 months prior to administration of study treatment, with the exception of a contraceptive implant.
28. Subjects with a history or presence (at screening or first baseline) of any clinically significant ECG abnormalities including, but not limited to any type pf AV blocks or any of the following ECG abnormalities on two or more tracings taken within 15 minutes at screening or baseline:
(a) PR greater than 200 msec.
(b) Any degree of atrio-ventricular block.
(c) QRS complex greater than 120 msec.
(d) QTcF greater than 470 msec (females) or greater than 450 msec (males).
(e) Prominent U waves or any significant morphological changes other than non-specific T-wave changes.
29. Subjects with a history or presence (at screening or first baseline) of any of the following cardiovascular findings:
(a) Clinically significant ventricular or supraventricular arrhythmia (as judged by the investigator).
(b) History or presence of coronary heart disease (stable or unstable), myocardial infarction, myocarditis, cardiomyopathy or heart failure.
(c) History or presence of long QT syndrome or any other cause of prolonged QT interval.
(d) History or cardiac catheter ablation.
(e) History or presence of symptomatic postural hypotension or syncopes.
30. Subjects with a family history of congenital long QT syndrome or unexplained sudden cardiac death.
31. Medications known to prolong the QTc interval.
32. Subjects with symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction less than 20%, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to study entry.
33. Subjects who are unable to return for all scheduled study visits.
Any other condition, that in the opinion of the investigator would render the subject unsuitable for enrolment, or could interfere with the subject participating in and completing the study.

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)
Subjects who meet the inclusion/exclusion criteria will be assigned a randomization number in the order of final eligibility for entry into the study using a randomization schedule generated prior to the start of the study. Subjects will be randomly assigned to receive either active or placebo. As this is a double blind, placebo controlled study, both the study personnel and subjects will be blinded as to which treatment they are to receive.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization using procedures like coin-tossing and dice-rolling.
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
The people analysing the results/data
Intervention assignment
Factorial
Other design features
This study will be conducted in two parts.
Part A will enrol 4 healthy volunteers. 3 healthy volunteers will receive the AKP-11 and 1 healthy volunteer will receive the placebo treatment.
Part B will enrol a total of 15 patients with mild to moderate psoriasis. 12 patients will receive the AKP-11 and 3 patients will receive the placebo treatment.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/12/2013
Actual
20/01/2014
Date of last participant enrolment
Anticipated
1/03/2014
Actual
21/08/2014
Date of last data collection
Anticipated
Actual
1/09/2014
Sample size
Target
19
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 7537 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 288214 0
Commercial sector/Industry
Name [1] 288214 0
Akaal Pharma Pty Ltd
Country [1] 288214 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Akaal Pharma Pty Ltd
Address
Chemistry Department, PS-3 #309-10
Plenty Rd, La Trobe University, Bundoora, VIC - 3086
Country
Australia
Secondary sponsor category [1] 286938 0
None
Name [1] 286938 0
Address [1] 286938 0
Country [1] 286938 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290124 0
The Alfred Ethics Committee
Ethics committee address [1] 290124 0
The Alfred Ethics Committee, The Alfred Hospital, 55 Commercial Road, Melbourne VIC 3004
Ethics committee country [1] 290124 0
Australia
Date submitted for ethics approval [1] 290124 0
28/10/2013
Approval date [1] 290124 0
19/11/2013
Ethics approval number [1] 290124 0

Summary
Brief summary
A Phase I, randomised, double blind, placebo-controlled, study of the safety, tolerability, pharmacokinetics and clinical activity of AKP-11 administration to healthy volunteers and patients with mild to moderate psoriasis.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 44082 0
Dr Jason Lickliter
Address 44082 0
Nucleus Network Ltd, Level 5, 89 Commercial Road, Melbourne VIC 3004
Country 44082 0
Australia
Phone 44082 0
1800 243 733
Fax 44082 0
+613 9076 8911
Email 44082 0
[email protected]
Contact person for public queries
Name 44083 0
Jason Lickliter
Address 44083 0
Nucleus Network Ltd, Level 5, 89 Commercial Road, Melbourne VIC 3004
Country 44083 0
Australia
Phone 44083 0
1800 243 733
Fax 44083 0
+613 9076 8911
Email 44083 0
[email protected]
Contact person for scientific queries
Name 44084 0
Gurmit S Gill
Address 44084 0
Chemistry Department, PS3, #309-10, La Trobe University, Bundoora, VIC -3086
Country 44084 0
Australia
Phone 44084 0
+613 9479 2584
Fax 44084 0
+613 9479 1266
Email 44084 0
[email protected]

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No Supporting Document Provided



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