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Trial registered on ANZCTR


Registration number
ACTRN12613000919718
Ethics application status
Approved
Date submitted
19/07/2013
Date registered
20/08/2013
Date last updated
28/11/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Parallel Arm Study of the Safety, Tolerability and Pharmacokinetics of Oral BTD-001 in Healthy Volunteers
Scientific title
A Phase 1, randomized, double-blind, placebo-controlled, 5 arm, parallel group study of the safety, tolerability and pharmacokinetics of oral BTD-001 in 30 male and female healthy volunteers
Secondary ID [1] 282828 0
NIL
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive impairment 289611 0
Condition category
Condition code
Neurological 290003 290003 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BTD-001 will be supplied as the active drug substance in powder form, for the Pharmacist to re-constitute as a concentrated stock solution.

To improve palatability and to preserve the double blind nature of the proposed trial, Balance has established that grape Kool-AID and orange TANG (provided by Balance) mask the bitterness of the drug substance. Subjects will be allowed to choose either Kool-AID or TANG and maintain that choice throughout the study. BTD-001 stock solution is diluted with 200mL of the fruit flavored drink by the pharmacist and administered at 4 dose levels:

25 mg
50 mg
100 mg
200 mg

Placebo will be Sterile, non pyrogenic Water for Irrigation, BP. One milliliter (1 mL) of placebo will be diluted in 200 mL of a fruit flavored drink (e.g., orange TANG or grape Kool AID) and consumed orally by the subject. The subject will remain on the same dose throughout the intervention period.

The pharmacist will prepare the BTD-001 stock solutions daily for the final drug product and placebo. The dosing period is a total of 7 consecutive days. On day 1 subjects receive a single dose of study medication in the AM. On Days 2-5, the pharmacist will dispense two doses for each subject, one to be consumed in the AM at the unit, and one to be consumed at home in the evening. Morning dose on Days 1, 2 and 7 is consumed at least 1 hour prior to breakfast; on Days 3-6 may be at least 1 hour prior to, or at least 2 hours after breakfast. The PM dose for days 2-6 is to be taken at least 2 hours after the evening meal. On day 6 the subject will receive both the AM and PM dose in the unit. On day 7 a single AM dose is administered in the unit.

Compliance for AM doses will be monitored and documented by site staff. compliance for PM doses not consumed in the unit will be determined by examining returned dosing containers and questioning the volunteer. Compliance will be documented in a binary form only - volunteer compliant yes or no.
Intervention code [1] 287569 0
Treatment: Drugs
Comparator / control treatment
Placebo (non pyrogenic water for irrigation BP) given daily over a 7 day period
Control group
Placebo

Outcomes
Primary outcome [1] 290003 0
Safety will be evaluated by:

-Collection of adverse events
-Physical and neurologic examination
-Vital signs (blood pressure, heart rate, temperature, respiratory rate)
-Weight
-Laboratory studies:
-Complete blood count (CBC) with differential and platelets
-Serum chemistry (including TSH)
-Urinalysis
-Pregnancy tests (females only)
-Electrocardiograms (ECG)
-State Trait Anxiety Inventory (State component only)
-Columbia Suicide Severity Rating Scale (Already Enrolled Subjects component only)

Twelve lead ECG will be performed following recommendations in ICH E14 regarding evaluation of QTc prolongation in patients in early stage clinical trials. ECGs will be performed in triplicate on Days 1, 2 and 7.

Known/possible adverse events include:
-Risk of seizure: individuals with a history of seizure (except for early single, uncomplicated early childhood febrile seizure) or neurologic disorders which might increase risk of seizure are excluded.

-Risk of psychiatric side effects: Individuals with a history of clinically significant (ie requiring medication or psychotherapy) depression or other psychiatric disorders within 2 years prior to the study are excluded. Subjects who report an adverse event of sadness or depression will be administered an unscheduled C-SSRS using the “Already Enrolled Subjects” version.

-Risk of cardiac events, individuals with a history of cardiac arrhythmias, a family history of prolonged QTc, or screening ECG abnormalities are excluded.
Timepoint [1] 290003 0
Change from baseline (Day1-14)
Secondary outcome [1] 303760 0
PK sampling of plasma will be conducted in all subjects at various time-points throughout the study.

The concentration of BTD-001 and two metabolites will be determined using a high-pressure liquid chromatography coupled with a mass spectrometer (LC/MS/MS) method.

Plasma samples may be retained, at Sponsor’s discretion, for possible analyses of additional BTD-001 metabolites at some future time.
Timepoint [1] 303760 0
Change from baseline (Day 1-14)

Eligibility
Key inclusion criteria
1. Healthy males and females as determined by medical history and physical examination between 18 and 35 years of age;
2. Written informed consent from the subject;
3. Able to comply with requirements for concomitant medications and consumption of caffeine, alcohol, tobacco and nicotine;
4. For females of child bearing potential, start date of their last menstrual period must be within 28 days of Day 1, first dose of study drug;
5. Sexually active females of childbearing potential must be willing to use a highly effective method of birth control from start of Screening until at least 3 months after last dose of study drug [defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, or some intrauterine contraceptive devices (IUDs);
-female partners of male study participants must use one of the following methods: Barrier contraceptive (e.g., female condom, cervical cap, diaphragm); Hormonal (oral, injectable, transdermal patch); or Intrauterine device; AND
-male participants must use condoms.
Minimum age
18 Years
Maximum age
35 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Weight <50 kg or > 110 kg;
2. BMI <18 kg/m2 or >35 kg/m2;
3. History of epilepsy, generalized convulsion or focal seizure (with exception of a single febrile seizure prior to 5 years of age);
4. Clinically significant (i.e., requiring medication or psychotherapy) psychiatric condition within the 2 years prior to Day 1, including but not limited to depression, bipolar disorder, generalized anxiety disorder, phobic disorders, panic disorder;
5. History of suicide attempt at any time, or of suicidal thinking within the last 6 months or behavior within the last 5 years reported on Screening Columbia Suicide Severity Rating Scale;
6. Personal or family history of congenital long QT syndrome or sudden death;
7. History of or current clinically significant or unstable neurological, psychiatric, cardiovascular, pulmonary, peripheral vascular, gastrointestinal, hepatic, endocrinological, hematological, or immunological conditions;
8. Any condition possibly affecting drug absorption (e.g., gastrectomy, vagotomy, or bowel resection);
9. Estimated glomerular filtration rate (eGFR) <90 mL/min by Cockroft Gault) at Screening or Baseline;
10. Screening or Baseline systolic blood pressure > 160 mm Hg or a diastolic blood pressure > 90 mm Hg (sitting or supine). One repeat measure is allowed to confirm eligibility;
11. Clinically significant abnormal electrocardiogram (ECG) at Screening or Baseline;
12. Clinically significant abnormalities in laboratory test results at Screening or Baseline;
13. Breastfeeding or pregnancy (females only);
14. Treatment with an investigational drug or biologic within 60 days preceding Day 1 (the first dose of study medication) or plans to take another investigational drug or biologic within 30 days of study completion;
15. Flu vaccination within 14 days of Day 1;
16. Blood donation or significant blood loss within 60 days prior to Day 1;
17. Plasma donation within 7 days of Day 1;
18. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this trial.

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)
All subjects, study personnel, study physician, and Balance Therapeutics staff will be blinded to study treatment throughout the course of the study. An unblinded pharmacist will be provided a randomization schedule with sufficient random code to prepare study medications for administration and distribution in each of the cohorts.

Emergency unblinding may be performed using the code-break envelopes supplied to the Principal Investigator at the site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated.
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
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis

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)
QLD
Recruitment postcode(s) [1] 7183 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 287647 0
Commercial sector/Industry
Name [1] 287647 0
Balance Therapeutics Pty Limited
Address [1] 287647 0
Nepean Highway, Mount Eliza, Victoria, 3930
Country [1] 287647 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Balance Therapeutics Pty Limited
Address
Nepean Highway, Mount Eliza, Victoria, 3930
Country
Australia
Secondary sponsor category [1] 286388 0
None
Name [1] 286388 0
Address [1] 286388 0
Country [1] 286388 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289616 0
Bellberry Limited
Ethics committee address [1] 289616 0
229 Greenhill Road
Dulwich SA 5065
Ethics committee country [1] 289616 0
Australia
Date submitted for ethics approval [1] 289616 0
17/04/2013
Approval date [1] 289616 0
18/06/2013
Ethics approval number [1] 289616 0
2013-04-165

Summary
Brief summary
This is a randomized, parallel arm, double-blind, placebo-controlled study. Subjects will be randomized to one of 5 arms, 4 dose levels of BTD-001 (25mg, 50mg, 100mg or 200mg) or placebo. Each arm consists of 6 subjects for a total of 30 subjects.

Subjects will complete a Screening period of up to 28 days, and will be admitted to the Clinical Research Unit (CRU) on Day -1. First dose will be administered on the morning of Day 1. Plasma samples for PK analyses, vital signs and ECGs will be collected at multiple time points on Days 1 and 2. To allow full PK characterization of the first dose, no evening dose will be administered on Day 1, though dosing will be BID subsequently.

Subjects will be discharged on Day 2 with their evening dose of medication and a diary card.
Subjects will report to clinic each morning on Days 3-6 for the AM dose of medication. On Days 3, 4 and 5, they will be issued with the evening dose and a diary card.

Subjects will be readmitted to the research unit of Day 6 and will receive the evening dose of study drug in the unit, approximately 12 +/- 1 hours prior to the scheduled AM dose for Day 7. Following the AM dose on Day 7, subjects will remain in the CRU for at least 8 hours, during which PK and safety measures will be collected. Subjects will then be discharged home.

A final Safety Follow Up visit will take place on Day 14, one week after the last dose of study drug.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41422 0
Dr Paul Griffin
Address 41422 0
Q-Pharm,Wayne Hooper Clinic
Clive Berghofer Cancer Research Centre (CBCRC)
Level 5, 300C Herston Road
Herston Qld 4006
Country 41422 0
Australia
Phone 41422 0
+61 (0)7 3845 3647
Fax 41422 0
Email 41422 0
p.griffin@qpharm.com.au
Contact person for public queries
Name 41423 0
Ms Kerensa Saljooqi
Address 41423 0
Balance Therapeutics Inc.
1250 Bayhill Drive,
San Bruno, CA 94066
Country 41423 0
United States of America
Phone 41423 0
+1 (650) 741-9100
Fax 41423 0
Email 41423 0
kerensa.saljooqi@balance-therapeutics.com
Contact person for scientific queries
Name 41424 0
Ms Kerensa Saljooqi
Address 41424 0
Balance Therapeutics Inc.
1250 Bayhill Drive,
San Bruno, CA 94066
Country 41424 0
United States of America
Phone 41424 0
+1 (650) 741-9100
Fax 41424 0
Email 41424 0
kerensa.saljooqi@balance-therapeutics.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