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Trial registered on ANZCTR


Registration number
ACTRN12615000873527
Ethics application status
Approved
Date submitted
21/07/2015
Date registered
21/08/2015
Date last updated
21/08/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Safety and Efficacy of THVD-102, a combination of Oxybutynin and Pilocarpine, in Subjects with Primary Focal Hyperhidrosis.
Scientific title
A Phase 2a Study Evaluating the Safety and Efficacy of THVD-102, a combination of Oxybutynin and Pilocarpine, in Subjects with Primary Focal Hyperhidrosis.
Secondary ID [1] 287095 0
THVD-102-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperhidrosis (excessive sweating) 295615 0
Condition category
Condition code
Skin 295892 295892 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
THVD-102, a combination of oxybutynin (7.5mg) and pilocarpine (7.5mg).

Run-In phase: open label Oxybutynin (5mg) twice daily for 21 days.
Double blind treatment periods: 3 treatment periods of 21 days where participants receive either of the following: THVD-102 administered twice daily as an oral capsule; Oxybutynin 7.5mg administered twice daily as an oral capsule; or Placebo administered twice daily as an oral capsule. Participants are randomised to one of the three doses for 21 days, and then cross-over to either of the two treatments for 21 days, with each treatment period preceding a washout period of at least 7 days.

Each participant will complete the run-in phase plus each of the 3 different treatment periods.

An IP dosing diary will be provided to participant to assist with compliance and dosing monitoring.
Intervention code [1] 292340 0
Treatment: Drugs
Comparator / control treatment
In the double blind phase the comparator is oxybutynin 7.5mg twice daily versus THVD-102 versus placebo.

Double blind treatment periods: 3 treatment periods of 21 days where participants receive either of the following: THVD-102 twice daily; oxybutynin 7.5mg twice daily; or Placebo twice daily. Participants are randomised to one of the three doses for 21 days, and then cross-over to either of the two treatments for 21 days, with each treatment period preceding a washout period of at least 7 days.
Control group
Active

Outcomes
Primary outcome [1] 295569 0
To evaluate the safety of THVD 102 (oxybutynin in combination with pilocarpine) in subjects with primary focal hyperhidrosis (axillary and/or palmar).

Safety will be evaluated through the following assessments:
Adverse events;
Clinical laboratory results (including pregnancy testing in women of child bearing potential);
Physical examinations;
Vital signs;
ECG measurements.
Timepoint [1] 295569 0
Adverse event information will be collected from the time of consent until 14 days after the last study drug administration.

Clinical laboratory tests will be assessed:
* Day -1 of oxybutynin run in and treatment period 1
* Day 21 of each treatment period (1, 2 and 3)
* Follow up visit


Physical Examination will be performed at:
*Day -1 of oxybutynin run-in and treatment period 1
* Day 21, treatment period 1, 2 and 3
* Follow up visit.

Vital Signs will be measured at:
* Day -1 of oxybutynin run in period and treatment period 1
* Day 0 of treatment period 2 and 3
* Day 21 of treatment period 1, 2 and 3
* Follow up

ECGs will be performed at:
* Day -1 of oxybutynin run-in and treatment period 1
* Day 21 of treatment period 1, 2 and 3
* Follow up

Primary outcome [2] 295682 0
To evaluate the efficacy of THVD 102 (oxybutynin in combination with pilocarpine) in subjects with primary focal hyperhidrosis (axillary and/or palmar).

This is a composite outcome and change in efficacy measurements include the following:
Hyperhidrosis Disease Severity Scale (HDSS); gravimetric measurements; rate of water vapor loss using a closed chamber device (Delfin Vapometer); hyperhidrosis Visual Quantification Scale; and hyperhidrosis Visual Analog Scale.
Timepoint [2] 295682 0
Measurements will be taken on Day -1 of Treatment Period 1, Day 0 of Treatment Periods 2 and 3 and on the last day of each Treatment Period
Secondary outcome [1] 315949 0
To evaluate symptoms of dry throat in subjects receiving THVD-102 (oxybutynin plus pilocarpine).
Timepoint [1] 315949 0
Measurements will be taken on Day -1 of Treatment Period 1, Day 0 of Treatment Periods 2 and 3 and on the last day of each Treatment Period. Measures will be taken using a visual analogue scale.
Secondary outcome [2] 316221 0
To evaluate symptoms of dry mouth in subjects receiving THVD-102 (oxybutynin plus pilocarpine).
Timepoint [2] 316221 0
Measurements will be taken on Day -1 of Treatment Period 1, Day 0 of Treatment Periods 2 and 3 and on the last day of each Treatment Period. Measures will be taken using a visual analogue scale.
Secondary outcome [3] 316222 0
To evaluate quality of life in subjects receiving THVD-102 (oxybutynin plus pilocarpine).
Timepoint [3] 316222 0
Modified Dermatology Life Quality Index questionnaire will be completed on Day -1 of Treatment Period 1, Day 0 of Treatment Periods 2 and 3 and on the last day of each Treatment Period.

Eligibility
Key inclusion criteria
1. Men or women
2. Able to provide written/signed informed consent
3. Age 18 to 70 (inclusive) years old at time of informed consent
4. Confirmed diagnosis of primary focal hyperhidrosis with axillary or palmar hyperhidrosis alone or in combination with another location (Hornberger)
Focal, visible, excessive sweating of at least six months duration without apparent cause with at least two of the following characteristics:
1. Bilateral and relatively symmetric
2. Impairs daily activities
3. Frequency of at least one episode per week
4. Age of onset less than 25 years
5. Positive family history
6. Cessation of focal sweating during sleep
5. Adequate renal and hepatic function:
a. Serum creatinine and estimated creatinine clearance < 1.5 x upper limit of normal range, and
b. ALT or AST <1.5 x upper limit of normal range
6. Negative serum pregnancy test for women of childbearing potential (WOCBP) within the 7 days prior to the first study treatment and a negative urine pregnancy test within the 1 day prior to the start of each subsequent treatment period
7. Women of childbearing potential (WOCBP) who are subjects and male subjects who are sexually active with WOCBP must agree to use 2 methods of highly effective contraception during the clinical trial
8. Willingness and ability to comply with the study protocol for the duration of the clinical trial
9. HDSS score of 3 or 4 at oxybutynin Run in Period Day -1 or Day -1 of Treatment Period 1 if completed the oxybutynin Run-In as a part of Study THVD 402-201.
10. A rating of “wet hands” or “dripping hands” on the Hyperhidrosis Visual Quantification Scale palmar for subjects with palmar hyperhidrosis or “wet” or “dripping” on the Hyperhidrosis Visual Quantification Scale axillary at Oxybutynin Run in Period Day -1 or Day -1 of Treatment Period 1 if completed the Oxybutynin Run-In as a part of Study THVD 402-201.
11. Dry Mouth or Dry Throat Visual Analog Scale (DM/TVAS) score of greater than or equal to 25 mm at Oxybutynin Run in Period Day 21. Subjects who participated in Study THVD 402 201 who have a documented DMVAS of at least 25mm following the Oxybutynin Run-In period do not need to complete the open label oxybutynin run in period in this trial; these subjects can begin this trial with Treatment Period 1.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant or breast feeding
2. QTc interval > 450 msec (males) > 475 msec (females)
3. Contraindication to oxybutynin and/or pilocarpine
a. Urinary retention or significant bladder outflow obstruction
b. Gastric retention, gastrointestinal obstructive disorder (e.g., pyloric stenosis), or decreased gastric motility
c. Narrow angle glaucoma or acute iritis
d. Myasthenia gravis
e. Asthma, chronic bronchitis or COPD requiring pharmacological therapy
f. Significant cardiovascular disease, including uncontrolled hypertension
g. Known or suspected cholelithiasis or biliary tract disease
h. Known or suspected renal colic or nephrolithiasis
i. Previous hypersensitivity to pilocarpine or oxybutynin
j. Any other condition in which administration of oxybutynin or pilocarpine may pose a significant risk to the patient
4. Botox Registered Trademark (onabotulinumtoxinA) treatment during the 8 months prior to screening or iontophoresis during the 2 months prior to screening
5. History of local surgical excision or laser removal (e.g. Miradry) of eccrine or apocrine glands of the axillae
6. Any reason, in the opinion of the investigator that a subject would not be a reliable subject and provide accurate data

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)
When eligibility is confirmed participants are enrolled and allocated to a treatment group. Fort this trial treatment allocation is concealed; i.e. containers are numbered and the investigator, site personnel and participant are unaware as to which treatment group they are assigned.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Crossover
Other design features
Three treatment triple cross over.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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)
WA

Funding & Sponsors
Funding source category [1] 291674 0
Commercial sector/Industry
Name [1] 291674 0
TheraVida, Inc
Address [1] 291674 0
177 Bovet Road, Sixth Floor
San Mateo, California, 94402
Country [1] 291674 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
TheraVida, Inc
Address
177 Bovet Road, Sixth Floor
San Mateo, California, 94402
Country
United States of America
Secondary sponsor category [1] 290351 0
Commercial sector/Industry
Name [1] 290351 0
Linear Clinical Research, Pty Ltd
Address [1] 290351 0
1st Floor, B Block, Hospital Avenue,
Nedlands WA 6009
Country [1] 290351 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293203 0
BellBerry Limited
Ethics committee address [1] 293203 0
129 Glen Osmond Road
Eastwood South Australia 5063
Ethics committee country [1] 293203 0
Australia
Date submitted for ethics approval [1] 293203 0
Approval date [1] 293203 0
12/03/2015
Ethics approval number [1] 293203 0

Summary
Brief summary
This research study will assess the safety and effectiveness of a THVD-102 which is a combination of 2 currently marketed drugs, oxybutynin (7.5mg) and pilocarpine (7.5mg).

The study will investigate if oxybutynin and delayed release pilocarpine together will reduce or eliminate the dry mouth side effect, whilst still reducing the symptoms of hyperhidrosis

This study will look at how effective THVD-102 is in reducing excessive sweating, as well as how safe and tolerable it is compared with either oxybutynin by itself or a placebo.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58802 0
Dr Janakan Krishnarajah
Address 58802 0
Linear Clinical Research
1st Floor, B Block, Hospital Avenue,
Nedlands WA 6009
Country 58802 0
Australia
Phone 58802 0
+61 8 9382 5100
Fax 58802 0
Email 58802 0
JKrishnarajah@linear.org.au
Contact person for public queries
Name 58803 0
Dr Benjamin F McGraw
Address 58803 0
TheraVida
177 Bovet Road, Sixth Floor
San Mateo, California, USA 94402
Country 58803 0
United States of America
Phone 58803 0
+1.650.638.2335
Fax 58803 0
Email 58803 0
ben@theravida.com
Contact person for scientific queries
Name 58804 0
Dr Benjamin F McGraw
Address 58804 0
TheraVida
177 Bovet Road, Sixth Floor
San Mateo, California, USA 94402
Country 58804 0
United States of America
Phone 58804 0
+1.650.638.2335
Fax 58804 0
Email 58804 0
ben@theravida.com

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