Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000243415
Ethics application status
Not yet submitted
Date submitted
1/05/2007
Date registered
7/05/2007
Date last updated
30/06/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1-2 Study for the Reduction of Submental Fat (Double Chin)
Scientific title
Phase 1-2, Multi-Centre, Randomised, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of ATX-101 (sodium deoxycholate for injection) for the reduction of subcutaneous fat in the submental area.
Secondary ID [1] 362 0
European Clinical Trials Database (EUDRACT): 2007-000146-13
Universal Trial Number (UTN)
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unwanted subcutaneous fat in the submental area 1780 0
Condition category
Condition code
Neurological 1867 1867 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Four arm study -Arm a: sodium deoxycholate injections of 0.5% Arm b: sodium deoxycholate injections of 1.0% Arm c: sodium deoxycholate injections of 2.0% Arm d: placebo. Subjects will receive up to 4 treatments of up to 24 injections (0.2mL each, or a maximum volume of approximately 4.8mL) per treatment (depending on size and configuration of the submental fat) which will be given at four week intervals.
Intervention code [1] 1732 0
Treatment: Drugs
Comparator / control treatment
Placebo
Control group
Placebo

Outcomes
Primary outcome [1] 2649 0
Primary Outcomes -Safety
The safety endpoints include:
1.Incidence, severity, and duration of all treatment-emergent adverse events
Timepoint [1] 2649 0
At each scheduled visit at weeks 0 (baseline), 1, 4, 5, 8, 9, 12, 13, 16, 20 and 24, the subject will undergo an examination of the injection sites and an interview in which they will be asked whether they have experienced any undesirable medical occurrence. Subjects may experience one or more of the following in the area around the injections: swelling, redness, pain immediately after the injection; burning, delayed tenderness, numbness, a feeling of skin tightness, itching, and bruising.
Primary outcome [2] 2650 0
Primary Outcomes -Safety
The safety endpoints include:
2. Incidence of study material-related adverse events
Timepoint [2] 2650 0
At each scheduled visit at weeks 0 (baseline), 1, 4, 5, 8, 9, 12, 13, 16, 20 and 24, the subject will undergo an examination of the injection sites and an interview in which they will be asked whether they have experienced any undesirable medical occurrence. Subjects may experience one or more of the following in the area around the injections: swelling, redness, pain immediately after the injection; burning, delayed tenderness, numbness, a feeling of skin tightness, itching, and bruising.
Primary outcome [3] 2651 0
Primary Outcomes -Safety
The safety endpoints include:
3. Severity and duration of study material-related adverse events
Timepoint [3] 2651 0
At each scheduled visit at weeks 0 (baseline), 1, 4, 5, 8, 9, 12, 13, 16, 20 and 24, the subject will undergo an examination of the injection sites and an interview in which they will be asked whether they have experienced any undesirable medical occurrence. Subjects may experience one or more of the following in the area around the injections: swelling, redness, pain immediately after the injection; burning, delayed tenderness, numbness, a feeling of skin tightness, itching, and bruising.
Primary outcome [4] 2652 0
Primary Outcomes -Safety
The safety endpoints include:
4. Changes from baseline (when treatment shall commence at week 0) in clinical laboratory (standard chemistry and haematology) and urinalysis test results
Timepoint [4] 2652 0
Assessed at weeks 4, 8, 12, 16 and 24.

At each scheduled visit at weeks 0 (baseline), 1, 4, 5, 8, 9, 12, 13, 16, 20 and 24, the subject will undergo an examination of the injection sites and an interview in which they will be asked whether they have experienced any undesirable medical occurrence. Subjects may experience one or more of the following in the area around the injections: swelling, redness, pain immediately after the injection; burning, delayed tenderness, numbness, a feeling of skin tightness, itching, and bruising.
Primary outcome [5] 2653 0
Primary Outcomes -Safety
The safety endpoints include:
5. Changes from baseline (week 0) in vital sign (sitting blood pressure, pulse, temperature and respiration) and weight measurements
Timepoint [5] 2653 0
Assessed at vosots in weeks 4, 8, 12, 16, 20 and 24. A full physical examination will be conducted prior to subject participation (screening visit) and again at the final visit at week 24.

At each scheduled visit at weeks 0 (baseline), 1, 4, 5, 8, 9, 12, 13, 16, 20 and 24, the subject will undergo an examination of the injection sites and an interview in which they will be asked whether they have experienced any undesirable medical occurrence. Subjects may experience one or more of the following in the area around the injections: swelling, redness, pain immediately after the injection; burning, delayed tenderness, numbness, a feeling of skin tightness, itching, and bruising.
Secondary outcome [1] 4503 0
Efficacy endpoints include change from baseline (when treatment will commence) in the Submental Fat Rating Scale, the Subject Satisfaction with Appearance Rating Scale, and the Subject Global Improvement Rating obtained at Visit 10 (week 16).
Timepoint [1] 4503 0
Secondary outcome [2] 4504 0
The secondary efficacy endpoints are the change from baseline in the Submental Fat and Skin Laxity rating scales at Visits 4, 6, 8, 10, and 12 (week 4, 8, 12, 16 and 24) as well as the change from baseline in the cervicaomental angle measured at Visit 10 (week 16).
Timepoint [2] 4504 0
Secondary outcome [3] 4505 0
Exploratory analyses of volumetric changes.
Timepoint [3] 4505 0
From baseline at visit 10 (week 16) will be conducted from ultrasonography obtained at a selected centre. As this is exploratory not all subjects will be selected at the site for this procedure.
Secondary outcome [4] 4506 0
This response rate by treatment group will be used to assess efficacy as a function of ATX-101 concentration.
Timepoint [4] 4506 0

Eligibility
Key inclusion criteria
Submental fat that is considered undesirable by the subject and graded by the investigator as 2 or 3 using the Submental Fat Rating Scale Males or nonpregnant, nonlactating females who are aged 25 to 55 years, inclusive, on the date of randomization. Females of childbearing potential must have a negative pregnancy test within 28 days before randomization and must agree to practice adequate contraception, in the judgment of the investigator, during the course of the trial.Body mass index of less than 35.0 kg/M2 determined within 28 days before randomization.History of maintenance of a stable body weight, in the judgment of the investigator, for at least 6 months before randomization.The subject is expected to comply with and understand the visit schedule and all of the protocol-specified tests and procedures.The subject is medically able to undergo the administration of study material as determined by clinical and laboratory evaluations obtained within 28 days before randomization including, but not limited to, liver function and creatinine test results that are in the normal range for the laboratory.Signed informed consent obtained before any study-specific procedure is conducted.
Minimum age
25 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of any intervention (e.g., liposuction, botulinum toxin injections) or trauma associated with the chin or neck areas.Loose skin in the neck or chin area for which reduction in submental fat may, in the judgment of the investigator, result in a cosmetically unacceptable outcome.Prominent platysmal bands at rest that interfere with the evaluation of submental fat.Evidence of any cause of enlargement in the submental area (e.g., thyroid enlargement, cervical adenopathy) other than localized submental fat.Fitzpatrick Skin Type IV, V, or VI (Appendix B).Currently on, or considering starting, a weight reduction regimen.History of cholecystectomy or current liver disease (e.g., acute or chronic hepatitis, cirrhosis). Presence of any coagulation disorder.Any medical condition (e.g., respiratory, cardiovascular, neurological disease, uncontrolled hypertension, thyroid dysfunction), that would interfere with the assessment of safety or efficacy in this trial or would compromise the ability of the subject to undergo study procedures or to give informed consent.History of treatment with deoxycholate-containing products (including amphotericin formulations containing deoxycholate or phosphatidylcholine/deoxycholate formulations).Treatment with fish oil, aspirin, or nonsteroidal anti-inflammatory agents (NSAIDS), except acetaminophen, within seven days before randomization, or any anticipated need for agents with anticoagulative effects during the course of the trial.Treatment with oral anticoagulants (e.g., warfarin or aspirin greater than 81 mg/day) within 28 days before randomization.Treatment with bile acid sequestrants (e.g., cholestyramine or colestipol) within 28 days before randomization.Treatment with radio frequency, laser procedures, chemical peel, or dermal fillers in the neck or chin area within 12 months before randomization.History of sensitivity to any components of the study material or to topical or local anesthetics (e.g., lidocaine, benzocaine, novocaine).Previous randomization into this trial.Treatment with an investigational device or agent within 30 days before randomization.

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 subject will be consented to the study (via witten informed consent) prior to any study-specific tests or proocedures. Randomisation via a central randomisation schedule by phone/fax. Subject considered enrolled once they have undergone randomisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be randomised in a 1:1:1:1 ratio via a randomization table created by a computer software (i.e., computerised sequence generation). The randomisation will be stratified according to the subjects baseline submental fat scale score.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This is a double blind study so the participant and Investigator administering the treatment will be blinded as well as those assessing outcomes. At the completion of the study unblinding will occur for the results to be analysed and reported.
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
72
Accrual to date
Final

Funding & Sponsors
Funding source category [1] 2015 0
Commercial sector/Industry
Name [1] 2015 0
Kythera Biopharmaceuticals Inc
Country [1] 2015 0
Primary sponsor type
Commercial sector/Industry
Name
Kythera Biopharmaceuticals Inc
Address
Country
United States of America
Secondary sponsor category [1] 1825 0
Commercial sector/Industry
Name [1] 1825 0
ICON Clinical Research Pty Ltd
Address [1] 1825 0
Country [1] 1825 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 3742 0
Bellbury Limited-Dr Greg Goodman and Associates
Ethics committee address [1] 3742 0
Leve 8, Trak Centre, 443-449 Toorak Road, Toorak VIC 3142
Ethics committee country [1] 3742 0
Australia
Date submitted for ethics approval [1] 3742 0
Approval date [1] 3742 0
Ethics approval number [1] 3742 0

Summary
Brief summary
Deoxycholic acid, or deoxycholate, is a naturally occurring bile acid produced by the liver as one of several end products of sterol metabolism. In the human body, deoxycholate serves to solubilise dietary fats and facilitate their absorption.
ATX-101 (sodium deoxycholate) is being developed by Kythera Biopharmaceuticals as a promising non-surgical treatment modality for several conditions characterised by unwanted or excessive fat deposition including, but not limited to, lipomas, lipodystrophy in patients with HIV infection, submental fat deposits (double chin) and other conditions for which liposuction or surgery are the current treatments. These surgeries are associated with the known risks of anaesthesia, infection, bleeding, bruising and scarring; the possibility of poor outcome, and the expected discomfort and “down-time” for the patient. Given the risks, which are well-established and documented, the growing popularity of these procedures is testament to the psychological importance of self image and to the benefit realised by subjects who seek them. The need for an approved, legitimate and minimally invasive medicinal product for reduction of localised fat deposits is substantiated by the significant and growing popularity of Lipostabil® and other unapproved extemporaneous mixtures of phosphatidylcholine/deoxycholate (PC/DC).
The objectives of this study are (1) to determine the safety and tolerability of ATX-101 injections at three concentrations relative to placebo; and (2) to evaluate the potential efficacy of ATX-101, relative to placebo, in reducing submental fat and thereby achieve improvement as judged by the Investigator and participant.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27835 0
Address 27835 0
Country 27835 0
Phone 27835 0
Fax 27835 0
Email 27835 0
Contact person for public queries
Name 10921 0
Alison Lai
Address 10921 0
Suite 201 Level 2, 2-4 Lyon Park Road North Ryde NSW 2113
Country 10921 0
Australia
Phone 10921 0
02 9859 3915
Fax 10921 0
Email 10921 0
[email protected]
Contact person for scientific queries
Name 1849 0
Alison Lai
Address 1849 0
Suite 201
Level 2
2-4 Lyon Park Road
North Ryde NSW 2113
Country 1849 0
Australia
Phone 1849 0
02 9859 3915
Fax 1849 0
Email 1849 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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