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Trial registered on ANZCTR


Registration number
ACTRN12617001251314
Ethics application status
Approved
Date submitted
22/08/2017
Date registered
28/08/2017
Date last updated
20/11/2019
Date data sharing statement initially provided
11/12/2018
Date results information initially provided
20/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Open-Label Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant (DLP-114)
Scientific title
Open-Label Study in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant (DLP-114)
Secondary ID [1] 292690 0
DLP-114
Universal Trial Number (UTN)
U1111-1200-9912
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Schizophrenia 304445 0
Bipolar Disorder I 304478 0
Autistic Disorder 304479 0
Condition category
Condition code
Mental Health 303773 303773 0 0
Autistic spectrum disorders
Mental Health 303822 303822 0 0
Other mental health disorders
Mental Health 303853 303853 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study duration for each subject involved in the study will be up to 202 days. This includes the following:
• Screening period (28 days)
• Oral risperidone (2 mg/day) – tolerability assessment (3 days);
• Oral risperidone (1 mg/day) – PK assessment (11 days);
• Washout (not less than 1 day, not more than 30 days);
• DLP-114 implant treatment (123 days);
• Follow-up (7 Days).

The study durg DLP-114 is a Risperidone Para-aminobenzoate Implant that is a combination drug-device product designed to continuously elute the equivalent of a daily 1 mg oral dose of risperidone following subcutaneous implantation.

The DLP-114 device will be implanted in the medial aspect of the upper arm halfway between the elbow and the shoulder, in line with the crease between the biceps and triceps muscles, using a sterile disposable implanter tool and local anesthesia in a minimally invasive procedure identical to that of other approved drug device products.
The device will remain implanted for 123 days.
Upon completion of the implant treatment period, the device will be removed by a qualified medical officer.





Intervention code [1] 298931 0
Treatment: Drugs
Intervention code [2] 298959 0
Treatment: Devices
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 303141 0
This study will assess the safety of DLP-114.
Safety will be determined by evaluating physical examinations, vital signs, ECGs, clinical laboratory parameters, and adverse events.
Timepoint [1] 303141 0
Blood samples for hematology, serum chemistry (fasted) to be collected at screening and prior to each oral risperidone dose during the oral risperidone treatment phase. Samples for this test during the implant treatment period will be collected at outpatient visits at Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, Day 84, Day 91, Day 98, Day 105, Day 112 and Day 126, Coagulation will only be performed at screening. Lipid panel (total cholesterol, LDL, HDL, non-HDL and triglycerides) will only be performed at screening, Day -15 (pre-dose), Day -1, Days 35, 63, 91 and 123. If lipid profile is clinically significant on Day 123, it will also be conducted on Day 130.
Full physical examination is performed at the screening visit. Abbreviated physical examinations will be performed at Day -15 to Day -13, Day -9, Day -1, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 49, Day 63, Day 77, Day 91, Day 105, and Day 123 and at Early Termination (if required).
Vital Signs are to be collected at: Screening, Day -15 to Day -13, Day -9, Day - 5, Day -2 to Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, Day 84, Day 91, Day 98, Day 105, Day 112, Day 123 to 124, Day 126, Day 130 and at ET (if required).
12-Lead ECG are to be collected at: Screening, Day -15 to Day -13, Day -1 to Day 2, Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 49, Day 63, Day 77, Day 91, Day 105, Day 123, Day 130 and at ET (if required).
AE and ADEs will be monitored throughout the study.
Primary outcome [2] 303178 0
This study will also assess the tolerability of DLP-114.
Local tolerance at the implantation site will be examined and scored for severity of visible signs of irritation/inflammation.
Implantation site inspection will be by visual examination at each assessment visit. Healing of the incision will be monitored. Dermal reactions will be scored on a skin irritation scale. Skin Irritation Scoring System recommended for transdermal dosage forms that describes the amount of erythema, edema, and other features indicative of irritation.

Skin Irritation Scoring System:
Dermal Response:
0 = no evidence of irritation
1 = minimal erythema, barely perceptible
2 = definite erythema, readily visible; minimal edema or minimal popular response
3 = erythema and papules
4 = definite edema
5 = erythema, edema, and papules
6 = vesicular eruption
7 = strong reaction spreading beyond test site
Other Effects:
A = slight glazed appearance
B = marked glazing
C = glazing with peeling and cracking
F = glazing with fissures
G = film of dried serous exudate covering all or part of the patch* site
H = small petechial erosions and/or scabs
Timepoint [2] 303178 0
Implant tolerability will be assessed at Day 1 to Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, Day 84, Day 91, Day 98, Day 105, Day 112, Day 123 to 124, Day 126, Day 130, at ET (if required).
Secondary outcome [1] 338014 0
Measure the plasma concentration of risperidone following repeated oral administrations:
PK parameters to be calculated for oral administrations include:
• Maximum concentration (Cmax);
• Minimum concentration (Cmin)
• Time to maximum concentration (Tmax);
• Time to minimum concentration (Tmin)
• Average concentration (Cave)
• Terminal half-life (t1/2)
Timepoint [1] 338014 0
PK collection time points are:
Day -2 at -0.17 hours, 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours (Day -1) and at ET (if required)..
Secondary outcome [2] 338015 0
Measure the plasma concentration of 9-OH risperidone following repeated oral administrations:
PK parameters to be calculated for oral administrations include:
• Maximum concentration (Cmax);
• Minimum concentration (Cmin)
• Time to maximum concentration (Tmax);
• Time to minimum concentration (Tmin)
• Average concentration (Cave)
• Terminal half-life (t1/2)

Timepoint [2] 338015 0
PK collection time points are:
Day -2 at -0.17 hours, 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours (Day -1) and and at ET (if required)..
Secondary outcome [3] 338016 0
Measure the plasma concentration of active moiety (risperidone + 9 OH risperidone) following repeated oral administrations:
PK parameters to be calculated for oral administrations include:
• Maximum concentration (Cmax);
• Minimum concentration (Cmin)
• Time to maximum concentration (Tmax);
• Time to minimum concentration (Tmin)
• Average concentration (Cave)
• Terminal half-life (t1/2)
Timepoint [3] 338016 0
PK collection time points are:
Day -2 at -0.17 hours, 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours (Day -1) and at ET (if required).
Secondary outcome [4] 338146 0
Measure the plasma concentration of risperidone following switch from oral risperidone to subcutaneous implantation of one DLP-114 device.
PK parameters to be calculated for implant treatment period include:
• Maximum concentration (Cmax);
• Minimum concentration (Cmin)
• Time to maximum concentration (Tmax);
• Time to minimum concentration (Tmin);
• Average concentration (Cave)
• Terminal half-life (t1/2). (PK) Analysis
Timepoint [4] 338146 0
PK collection time points are: on Day 1 at 1, 2, 3, 4, 6, 8, 12, 24 hours (Day 2), 28 hours (Day 2), 32 hours (Day 2), 36 hours (Day 2), 48 hours (Day 3), 52 hours (Day 3), in the morning of Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, Day 84, Day 91, Day 98, Day 105, Day 112, and Day 123 (at -1 hour, 1, 2, 3, 4, 6, 8, 12, 48 hours – Day 124), Day 126 (morning), and at ET (if required).

Secondary outcome [5] 338147 0
Measure the plasma concentration of 9-OH risperidone following switch from oral risperidone to subcutaneous implantation of one DLP-114 device;
PK parameters to be calculated for implant treatment period include:
• Maximum concentration (Cmax);
• Minimum concentration (Cmin)
• Time to maximum concentration (Tmax);
• Time to minimum concentration (Tmin);
• Average concentration (Cave)
• Terminal half-life (t1/2). (PK) Analysis
Timepoint [5] 338147 0
PK collection time points are: on Day 1 at 1, 2, 3, 4, 6, 8, 12, 24 hours (Day 2), 28 hours (Day 2), 32 hours (Day 2), 36 hours (Day 2), 48 hours (Day 3), 52 hours (Day 3), in the morning of Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, Day 84, Day 91, Day 98, Day 105, Day 112, and Day 123 (at -1 hour, 1, 2, 3, 4, 6, 8, 12, 48 hours – Day 124), Day 126 (morning), and at ET (if required).
Secondary outcome [6] 338148 0
Measure the plasma concentration of active moiety (risperidone + 9 OH risperidone) following switch from oral risperidone to subcutaneous implantation of one DLP-114 device;
PK parameters to be calculated for implant treatment period include:
• Maximum concentration (Cmax);
• Minimum concentration (Cmin)
• Time to maximum concentration (Tmax);
• Time to minimum concentration (Tmin);
• Average concentration (Cave)
• Terminal half-life (t1/2). (PK) Analysis
Timepoint [6] 338148 0
PK collection time points are: on Day 1 at 1, 2, 3, 4, 6, 8, 12, 24 hours (Day 2), 28 hours (Day 2), 32 hours (Day 2), 36 hours (Day 2), 48 hours (Day 3), 52 hours (Day 3), in the morning of Day 4, Day 7, Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, Day 84, Day 91, Day 98, Day 105, Day 112, and Day 123 (at -1 hour, 1, 2, 3, 4, 6, 8, 12, 48 hours – Day 124), Day 126 (morning), and at ET (if required).
Secondary outcome [7] 338149 0
Amount of unreleased drug substance remaining in the DLP-114 implant following its removal in order to estimate average daily output.
Timepoint [7] 338149 0
The devices will be weighed prior to use. At the end of the study, the devices be opened and the residual drug will be measured using a specific digestion process and HPLC analytics to measure potency

Eligibility
Key inclusion criteria
Healthy adult male and non-pregnant females
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known hypersensitivity to titanium, implant materials or procedure;
2. Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the amide type (local anesthetic used during implant and explant procedures);
3. History of abnormal scar formation or family history of keloid formation;
4. Disorders of the central nervous system, including psychiatric disorders, behavioral disturbances, cerebrovascular events, depression, bipolar disorder, migraine, Parkinson’s disease.
5. History of treatment for marked depression, anxiety, tension, or agitation; currently on medication for asthma; use of any MAOI within 14 days prior to dosing; history of surgery requiring anesthesia within 8 weeks prior to start of dosing;
6. Blood or plasma donation within 30 days prior to start of dosing. All subjects will be advised not to donate blood or plasma for six weeks after completing the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
This is an open-label study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Safety/Tolerability Data:
The percentage of subjects with treatment-emergent Adverse Events will be summarized for each treatment. Laboratory data will be summarized by the type of laboratory test. Normal reference ranges and markedly abnormal results will be used in the summary of laboratory data. Raw data and change from baseline in clinical laboratory parameters will be summarized using descriptive statistics. A listing of subjects with any laboratory results outside the reference ranges that are deemed clinically significant will be provided.

Pharmacokinetic Data:
Listing of individual subject plasma concentrations, actual blood sampling times, and PK parameters and graphs of concentration vs. time will be prepared by study treatment. Plasma concentrations and PK parameters will be summarized by and compared between study treatments using descriptive statistics. Statistical analysis will be performed on the pharmacokinetic parameters using validated statistical software.

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 in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 8832 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 16962 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 297332 0
Commercial sector/Industry
Name [1] 297332 0
Delpor Australia Pty Ltd
Address [1] 297332 0
Level 2,
139 Frome Street,
Adelaide, SA, 5000

Country [1] 297332 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Delpor Australia Pty Ltd
Address
Level 2,
139 Frome Street,
Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 296305 0
Commercial sector/Industry
Name [1] 296305 0
CPR Pharma Services Pty Ltd
Address [1] 296305 0
28 Dalgleish Street,
Thebarton, Adelaide,
South Australia, 5031
Country [1] 296305 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298433 0
Bellberry Ltd
Ethics committee address [1] 298433 0
129 Glen Osmond Road
Eastwood
South Australia 3063
Ethics committee country [1] 298433 0
Australia
Date submitted for ethics approval [1] 298433 0
07/07/2017
Approval date [1] 298433 0
28/08/2017
Ethics approval number [1] 298433 0
2017-06-491

Summary
Brief summary
This study is a first-in-man clinical study of DLP-114, a Risperidone Para-aminobenzoate Implant product. The study is an open-label, single sequence design aimed at assessing the safety and tolerability of DLP-114 and evaluating its utility in achieving a PK profile that is comparable to the marketed oral form of risperidone.

Healthy volunteers will be enrolled implanted with DLP-114 in groups of up to 3 volunteers per group. The first group of 3 healthy volunteers to receive the DLP-114 implant will be a sentinel group. The safety and tolerability of the DLP-114 implant will be assessed in the sentinel group for at least 28 days prior to any other volunteers being dosed implanted with DLP-114 in the study. Only if the safety and tolerability data, obtained from the sentinel group, are considered acceptable by the investigator and the sponsor, will the remainder of healthy volunteers commence implant treatment in the study.

Treatment of each subject will be conducted in five sequential periods:
1. Oral risperidone (2 mg/day) – tolerability assessment;
2. Oral risperidone (1 mg/day) – PK assessment;
3. Washout;
4. DLP-114 implant treatment;
5. Follow-up.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77070 0
Dr Nicholas Farinola
Address 77070 0
CMAX – Clinical Research Pty Ltd,
Level 5, 18a North Terrace, Adelaide,
South Australia, 5000, Australia
Country 77070 0
Australia
Phone 77070 0
+61 (8) 7088 7900
Fax 77070 0
+61 (8) 7088 7999
Email 77070 0
nicholas.farinola@sa.gov.au
Contact person for public queries
Name 77071 0
Dr Nicholas Farinola
Address 77071 0
CMAX – Clinical Research Pty Ltd,
Level 5, 18a North Terrace, Adelaide,
South Australia, 5000, Australia
Country 77071 0
Australia
Phone 77071 0
+61 (8) 7088 7900
Fax 77071 0
+61 (8) 7088 7999
Email 77071 0
nicholas.farinola@sa.gov.au
Contact person for scientific queries
Name 77072 0
Dr Nicholas Farinola
Address 77072 0
CMAX – Clinical Research Pty Ltd,
Level 5, 18a North Terrace, Adelaide,
South Australia, 5000, Australia

Country 77072 0
Australia
Phone 77072 0
+61 (8) 7088 7900
Fax 77072 0
+61 (8) 7088 7999
Email 77072 0
nicholas.farinola@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary