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Trial registered on ANZCTR


Registration number
ACTRN12624000341527
Ethics application status
Approved
Date submitted
28/02/2024
Date registered
26/03/2024
Date last updated
21/04/2024
Date data sharing statement initially provided
26/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Bioequivalence Assessment of Topical Smartech 2% Diclofenac Sodium Solution Compared to a Reference Product When Applied to the Knees of Healthy Male and Female Participants
Scientific title
Bioequivalence Assessment of Topical Smartech 2% Diclofenac Sodium Solution (Formulation 2) Compared to a Reference Product (2% Diclofenac Sodium Solution) When Applied to the Knees of Healthy Male and Female Participants
Secondary ID [1] 311537 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record
Participants from ACTRN12622001391763 will be invited to participate in Group 1 of this study to receive Smartech Formulation 2 investigational product.

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis of the knee 332890 0
Condition category
Condition code
Musculoskeletal 329606 329606 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will investigate the bioequivalence of Smartech Formulation 2 when compared with a reference product (either Pennsaid 2% diclofenac or a generic diclofenac 2%) as described below:
Group 1: Participants who were treated with Pennsaid and were included in the study PK population in the SMTPK001 study (ACTRN12622001391763), and to whom only Smartech Formulation 2 will be administered in this study
Group 2: Participants who were not treated in the SMTPK001 study (ACTRN12622001391763), and to whom Smartech Formulation 2 and generic diclofenac 2% will be administered in this study following a crossover design, with a washout period between treatments of at least 14 days and up to 17 days.
Smartech Formulation 2 (diclofenac sodium topical solution) 2 percent weight for weight (w/w) is a topical non-steroidal anti-inflammatory drug. Two pump actuations (2mL, equivalent to 40mg diclofenac) will be applied to each knee, twice daily for 7.5 days. On Day 8 of the study, two pump actuations (2mL equivalent to 40mg diclofenac) will be applied once.
The investigational product will be applied to both knees, within an area of 10cm above and below the knee, front and back by a clinical trial nurse. All doses will be applied while the participant is a resident of the clinical trial unit. The clinical trial nurse will actuate the pump onto the hand and apply the product to the participant knees. One knee will be dosed and then the other ensuring two pumps are applied fully to each knee. The knees will be allowed to dry before clothing or bed linen are allowed to touch the area of application.
In Group 2, a washout period of at least 14 days and up to 17 days is scheduled between the dosing periods of Smartech Formulation 2 and the reference generic product.


Intervention code [1] 327994 0
Treatment: Drugs
Comparator / control treatment
Reference product (Generic diclofenac sodium) topical solution 2 percent w/w, for topical use is a topical non-steroidal anti-inflammatory drug indicated for the treatment of the pain of osteo arthritis (OA) of the knee(s). The generic product is approved for use in the United States of America (USA).
Two pump actuations (2mL, equivalent to 40mg diclofenac) will be applied to each knee, twice daily for 7.5 days. On Day 8 of the study, two pump actuations (2mL equivalent to 40mg diclofenac) will be applied once to each knee.
Control group
Active

Outcomes
Primary outcome [1] 337396 0
To determine the bioequivalence of Smartech Formulation 2 compared to reference generic product when administered twice daily to each knee.
Timepoint [1] 337396 0
The PK blood samples will be drawn at the following times:
Day 1: pre-morning dose, 0.5 hour after morning dose, 1 hour after morning dose, 2 hours from morning dose, 3 hours from morning dose, 4 hours from morning dose, 6 hours from morning dose, 8 hours from morning dose, 10 hours from morning dose, 12 hours form morning dose.
Day 2: pre morning dose (24 hours from first Day 1 dose)
Day 3: pre morning dose (48 hours from first Day 1 dose)
Day 4: pre morning dose (72 hours from first Day 1 dose)
Day 5: pre morning dose (96 hours from first Day 1 dose)
Day 6: pre morning dose (120 hours form first Day 1 dose)
Day 7: pre morning dose (144 hours from first Day 1 dose)
Day 8: pre morning dose, 0.5 hour after morning dose, 1 hour after morning dose, 2 hours from morning dose, 3 hours from morning dose, 4 hours from morning dose, 6 hours from morning dose, 8 hours from morning dose, 10 hours from morning dose, 12 hours form morning dose.
Day 9: 24 hours from Day 8 dose
Day 11: 72 hours from Day 8 dose
Day 13: 120 hours from Day 8 dose
Day 15: 168 hours from Day 8 dose
Secondary outcome [1] 431668 0
Collection of aesthetic descriptions for Smartech Formulation 2 and, as applicable, generic reference product.
Timepoint [1] 431668 0
The study questionnaire will be administered to participants on Day 1 and Day 8 (7 days following the first dose) of the study confinement period.
Secondary outcome [2] 431733 0
To evaluate the safety and tolerability of Smartech Formulation 2 following topical administration to each knee, twice daily, for 7.5 days. Assessment of each parameter will occur independently.
Timepoint [2] 431733 0
Adverse events will be collected by the study team from the time of informed consent until the Day 22 end of study telephone call.
Secondary outcome [3] 431734 0
To evaluate the safety and tolerability of Smartech Formulation 2 following topical administration to each knee, twice daily, for 7.5 days.
Timepoint [3] 431734 0
Blood and urine are collected for assessment in both study periods at the following times:
Screening visit (up to 28 days prior to first dosing)
Day -1 (day prior to first dosing)
Day 1 (first dose)
Day 4 (3 days after first dose)
Day 8 (7 days after first dose)
Day 15 (14 days after first dose, for Period 2 only)
Secondary outcome [4] 431735 0
To evaluate the safety and tolerability of Smartech Formulation 2 following topical administration to each knee, twice daily, for 7.5 days.
Timepoint [4] 431735 0
Vital signs data will be collected at Screening (up to 28 days prior to dosing day),
Day -1 (prior to dosing)
Days 1- 7 (during dosing) at 30 minutes prior to the morning dose, 2 hours after the morning dose, 6 hours after morning dose and 30 minutes prior to the evening dose
Day 8 (7 days after first dose) at 30 minutes prior to the morning dose
Days 9, 11, 13 and 15 (8, 10, 12 and 14 days after the first dose) prior to blood sample collection
Secondary outcome [5] 431745 0
To evaluate the safety and tolerability of Smartech Formulation 2 following topical administration to each knee, twice daily, for 7.5 days.
Timepoint [5] 431745 0
ECG will be collected at Screening (up to 28 days prior to first dose)
Day -1. (1 day prior to the first dose)
Day 1 at 6 hours after the morning dose
Day 8 (7 days after first dosing day) at 6 hours after the morning dose
Day 15 (14 days after the first dose) prior to blood sampling
Secondary outcome [6] 431746 0
To evaluate the safety and tolerability of Smartech Formulation 2 following topical administration to each knee, twice daily, for 7.5 days.
Timepoint [6] 431746 0
A full physical examination will be performed at the time of screening (up to 28 days prior to first dose)
A symptom directed physical examination will be conducted on the patient at the following times:
Day -1 (day prior to dosing)
Days 1 - 8 (as needed after dosing)
Day 15 (14 days after the first dose) (cohort 2, period 1, as needed)
A full physical examination will be conducted on Day 15 (14 days after the first dose) (cohort 1 and cohort 2, period 2)
Secondary outcome [7] 431747 0
To evaluate the safety and tolerability of Smartech Formulation 2 following topical administration to each knee, twice daily, for 7.5 days.
Timepoint [7] 431747 0
Skin assessment will be conducted at the following times:
Day 1 to Day 8 (7 days after the first dose) - 30 minutes prior to the morning dose each day and 6 hours after the morning dose.

Eligibility
Key inclusion criteria
1. Have signed and dated a Human Research Ethics Committee (HREC)-approved informed consent.
2. Are between 18 – 55 years of age (inclusive) at the time of informed consent signature.
3. Have a body mass index (BMI) between 19 to 32 kg per m2 at Screening and at CRU admission on Day -1 for the first Study Period, as applicable.
4. Are nonsmokers (including tobacco, e-cigarettes or equivalent) for at least 1 month prior to planned first study drug administration, and are willing to not smoke while confined at the CRU.
5. Are medically healthy without clinically significant (in the opinion of the Investigator (or qualified designee) abnormalities at Screening and at CRU admission on Day -1 for the first Study Period, as applicable, including:
Full physical examination without any clinically relevant findings at the discretion of the Investigator (or qualified designee);
Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg as measured after at least 5 minutes in a supine, semi-reclined or seated position;
Heart rate (HR) in the range of 45 to 100 bpm as measured after at least 5 minutes rest in a supine, semi-reclined or seated position;
Body temperature (tympanic), between 35.5 and 37.7 degrees Celcius;
No clinically significant findings at the discretion of the Investigator (or qualified designee) in clinical chemistry, haematology, coagulation and urinalysis tests;
Triplicate 12-lead ECG, taken after at least 5 minutes in a supine, semi-reclined or seated position, with a QT interval corrected using the Fridericia method (QTcF) less than or equal to 450 msec for males and less than or equal to 470 msec for females and no clinically significant abnormalities as judged by the Investigator (or qualified designee).
6. Female participants must be of nonchildbearing potential or if women of childbearing potential (WOCBP), must agree not to donate ova, not to attempt to become pregnant and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method of contraception from signing the consent form until at least 30 days after the last dose of the study drug.
7. Male participants must agree not to donate sperm and, if engaging in sexual intercourse with a partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
8. All their safety laboratory values at Screening and CRU admission (Day -1 for the first Study Period, as applicable) fall within local laboratory reference ranges or are designated by the Investigator (or qualified designee) to be not clinically significant.
9. Agree to abstain from prescription medication and dietary supplements and over the counter (OTC) medications, from 14 days prior to CRU admission through to study completion,
10. Agree to abstain from alcohol from 3 days prior to CRU admission (Day -1 for each Study Period, as applicable), at least 12 hours ahead of each visit, and during the confinement period.
11. Agree to abstain from shaving, waxing or using any hair removal technique from the knee area within 7 days of CRU admission on Day -1 for each Study Period, as applicable. Laser hair removal is not allowed within 90 days of CRU admission on Day -1 for the first Study Period, as applicable. The use of a hair clipper with guard is allowable before the Treatment Period at any time up to and including CRU admission on Day -1 (for each Study Period, as applicable).
12. Agree to avoid exposure to natural or artificial sunlight on treated knees while confined at the CRU from Day -1 for each Study Period, as applicable, and up to at least 4 days following last treatment.
13. Agree to avoid covering the knee with clothing until the knee is completely dry following study drug administration; not to exercise and not to use heating pads, during the Treatment Period and for at least 4 days following the last treatment, for each Study Period (as applicable).
14. Have the ability to understand the requirements of the study and are willing to comply with all study procedures, as judged by the Investigator (or qualified designee).
15. Are considered healthy, have 2 treatable knees as assessed by the Investigator and have no clinically significant illnesses or conditions or have used prior therapies that would prevent inclusion in the study as determined by the Investigator.
16. Agree not to consume poppy seeds from at least 3 days prior to any scheduled CRU visits (including Screening). They agree not to conduct any strenuous exercise (including weightlifting) in the 72 hours prior to any scheduled visits and while at the CRU.
17. Agree not to use moisturiser, creams, lotions, sunscreen or any other topical solution/gel/lotion/product applied to knees for the duration of the study.
18. Agree to abstain from consuming caffeine and xanthene products (e.g., coffee, tea, chocolate, and caffeine-containing sodas, colas) for at least 24 hours prior to clinical visits, and while at the CRU.
19. Agree to avoid tattooing in the knee area during the study.
Inclusion criterion to be applied to Cohort 1 only:
20. Have previously participated in the SMTPK001 study and have completed the Pennsaid treatment period per study protocol and were included in the study PK population.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants are not eligible for participation in the study if they meet any of the following criteria:
1. Have a known hypersensitivity to diclofenac sodium, salicylates or other NSAIDs.
2. Have a history of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
3. Have risk factors for cardiovascular thrombotic events; known cardiovascular disease or risk factors for cardiovascular disease.
4. Have had a coronary artery bypass graft surgery within the past 12 months.
5. In the opinion of the Investigator, they have a history of or risk factors for serious gastrointestinal events including peptic ulcer disease or gastrointestinal tract bleeding (cholecystectomy and Gilbert’s Syndrome acceptable).
6. Have a history of gastric bypass surgery.
7. Have used tanning product within 14 days of CRU admission (Day -1 for the first Study Period, as applicable), and/or have had a current or recent unresolved sunburn within 14 days of CRU admission (Day -1 for the first Study Period, as applicable), in the area designated for study drug application.
8. Have any skin condition(s), open wounds in the knee area, and/or any irregularities of the skin in the knee area (i.e. post-surgical or excessive scarring, and/or tattoos and/or any permanent cosmetic visual alteration [i.e. cosmetic scarification]), or amount of hair, which in the opinion of the Investigator (or qualified designee) would:
a. impact absorption of the investigational product and/or,
b. prevent any AEs from being reported.
Note: in case of hair around the knee that the Investigator (or qualified designee) deems may impact point a. and/or b. above, they may choose to allow the use of a hair clipper with guard at any time before the Treatment Period up to and including admission on Day -1 for each Study Period, as applicable.
9. Have or are planning to donate more than 100 mL of blood or plasma within 30 days prior to planned first study drug administration, and/or have lost more than 500 mL of whole blood within 30 days prior to planned first study drug administration, and/or have received a blood transfusion within 1 year of planned first study drug administration.
10. Have a history of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) within 12 weeks prior to Screening, as assessed by the Investigator (or qualified designee).
11. Have a positive test for drugs of abuse (including marijuana) and/or breath alcohol test result at Screening or at CRU admission (Day -1 of the first Study Period, as applicable). Retest is allowable at the discretion of Investigator (or qualified designee).
12. Have a positive cotinine test at Screening or admission to the CRU (Day -1 of the first Study Period, as applicable).
13. Have a creatinine clearance (CrCl) < 80 mL/min calculated using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the upper limit of normal (ULN).
14. Have a clinical history of chronic kidney disease (CKD).
15. Have liver function test results elevated more than 1.5-fold above the ULN for gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Participants with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator (or qualified designee), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
16. Have liver function tests more than 1.5-fold above the ULN for bilirubin (total, direct and indirect).
17. Have positive test results for human immunodeficiency virus (HIV-1 or HIV-2) antibody/antigen, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the Screening visit. Participants who have no evidence of cirrhosis and have completed a curative intent regimen for HCV, with a negative HCV polymerase chain reaction (PCR) test, will not be excluded.
18. Have a known hypersensitivity to any of the study drug ingredients.
19. Have had any vaccinations within 14 days prior to the planned first study drug administration.
20. For WOCBP, they have a positive serum pregnancy test at Screening or a positive urine pregnancy test (with confirmatory serum pregnancy test) at admission (Day -1 of the first Study Period, as applicable).
21. Are females who are breastfeeding or planning to breastfeed at any time during the study.
22. Have participated in another clinical trial of an investigational drug within 30 days or 5 half-lives of the investigational agent (whichever is longer) prior to the planned first study drug administration.
Exclusion criterion to be applied to Cohort 2 only:
23. Have previously participated in the SMTPK001 study (relevant to Cohort 2)

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
27/03/2024
Actual
27/03/2024
Date of last participant enrolment
Anticipated
14/07/2024
Actual
Date of last data collection
Anticipated
31/07/2025
Actual
Sample size
Target
90
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 26182 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 42054 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 315832 0
Commercial sector/Industry
Name [1] 315832 0
Smartech Topical AU Pty Ltd
Country [1] 315832 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Smartech Topical AU Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 317973 0
None
Name [1] 317973 0
Address [1] 317973 0
Country [1] 317973 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314689 0
Bellberry Human Research Ethics Committee B
Ethics committee address [1] 314689 0
https://bellberry.com.au/
Ethics committee country [1] 314689 0
Australia
Date submitted for ethics approval [1] 314689 0
13/12/2023
Approval date [1] 314689 0
29/01/2024
Ethics approval number [1] 314689 0

Summary
Brief summary
This study is designed as an open-label study to evaluate the PK profile, comparative bioequivalence, safety, and tolerability of Smartech Formulation 2 (2 percent w/w diclofenac sodium topical solution) and diclofenac 2%, applied to both knees of healthy adult male and female participants twice a day for 7.5 days.
The study will be conducted in up to 90 evaluable participants. Evaluable participants are defined as those who have completed a treatment period with diclofenac 2% and a treatment period with Formulation 2, with a washout period between the 2 treatments of at least 14 days. These participants may be by either:
Participants who were treated with Pennsaid and were included in the study PK population in the SMTPK001 study, and to whom only Smartech Formulation 2 will be administered in this study,
or
Participants who were not treated in the SMTPK001 study, and to whom Smartech Formulation 2 and diclofenac 2% will be administered in this study following a crossover design, with a washout period between treatments of at least 14 days.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132402 0
Dr Jonathan Newchurch
Address 132402 0
CMAX Clinical Research, 21-24 North Terrace, Adelaide SA 5000
Country 132402 0
Australia
Phone 132402 0
+61 870887900
Fax 132402 0
Email 132402 0
[email protected]
Contact person for public queries
Name 132403 0
Tom Hnat
Address 132403 0
Smartech Topical AU Pty Ltd, 58 Gipps St, Collingwood VIC 3066
Country 132403 0
Australia
Phone 132403 0
+16194497388
Fax 132403 0
Email 132403 0
[email protected]
Contact person for scientific queries
Name 132404 0
Tom Hnat
Address 132404 0
Smartech Topical AU, 58 Gipps St, Collingwood VIC 3066
Country 132404 0
Australia
Phone 132404 0
+16194497388
Fax 132404 0
Email 132404 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Sponsor decision


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.