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Trial registered on ANZCTR


Trial ID
ACTRN12612000696897
Ethics application status
Approved
Date submitted
28/06/2012
Date registered
29/06/2012
Date last updated
22/05/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
A trial of BIT225 in patients with HIV-1 infection, to study the safety, concentration and distribution in the body, and anti-viral activity of the drug.
Scientific title
A Phase 1, Placebo-Controlled, Randomised Study of the Safety, Pharmacokinetics and Antiviral Activity of BIT225 in Patients with Human ImmunodeficiencyVirus-1 Infection.
Secondary ID [1] 280746 0
BIT225-004
Universal Trial Number (UTN)
U1111-1132-1771
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Human Immunodeficiency Virus-1 infection 286799 0
Condition category
Condition code
Infection 287107 287107 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BIT225, 400mg oral, once daily on days 1 and 10, and twice daily on days 2 to 9. BIT225 is supplied as a powder to be suspended immediately before use in 25mL of OraSweet Sugar Free, a taste masking solution. After administration the patient will be asked to drink 240mL of non-carbonated water, which is poured into the dosing cup and swirled around to collect the remaining powder, before drinking.
Intervention code [1] 285174 0
Treatment: drugs
Comparator / control treatment
Placebo is 400mg of lactose to be suspended immediately before use in 25mL of OraSweet Sugar Free, a taste masking solution. After administration the patient will be asked to drink 240mL of non-carbonated water, which is poured into the dosing cup and swirled around to collect the remaining powder, before drinking.
Control group
Placebo

Outcomes
Primary outcome [1] 287429 0
Evaluate the safety and tolerability of 400mg BIT225 twice daily compared to placebo in patients with human immunodeficiency virus-1 (HIV-1) infection that are antiretroviral niave. Safety and tolerability will be assessed by comparison to placebo of treatment emergent untoward medical changes, e.g. nausea, vomitting or loss of weight, and changes in clinical laboratory assessments, vital signs, and ECG.
Timepoint [1] 287429 0
Evaluated daily over 10 days dosing, and continuing to day 20 (10 days post dose).
Secondary outcome [1] 298127 0
Evaluate the pharmacokinetics of 400mg BIT225 administered daily on days 1 and 10, and twice daily on days 2 to 9 (for 10 consecutive days) in patients with HIV-1 infection
Timepoint [1] 298127 0
Pharmacokinetic samples will be collected on Days 1, 2 and 5, then on days 10, 11 and 12. The concentration of BIT225 in plasma will be measured using a validated liquid chromatography tandem mass spectrometry method.
On days 1 and 10 samples will be collected 30-60 minutes pre-dose, then 30, 60, 90 and 120 minutes, and 3 and 4 hours post dose. On day 10 additional samples will be taken at 6, 8, 10 and 12 hours post dose. On days 2 and 11 a sample will be taken at 24 hours post dose. On day 5 a sample will be collected predose and on day 12 48 hours post dose.
Secondary outcome [2] 298128 0
Evaluate the antiviral activity of BIT225 administered for 10 consecutive days in patients with HIV-1 infection that are antiretroviral therapy naive. Change from baseline plasma viral load will be measured using the Roche COBAS TaqMan HIV-1 test, i.e. PCR.
Timepoint [2] 298128 0
Plasma HIV RNA will be measured on days 1, 2, 5, 10, 11 and 20
Secondary outcome [3] 298129 0
Evaluate BIT225 levels in cerebrospinal fluid will be measured using a validated liquid chromatography tandem mass spectrometry method.
Timepoint [3] 298129 0
Day 9 or 10, depending on the availability of the participant.

Eligibility
Key inclusion criteria
1. Males or females aged 18 to 65 years.

2. HIV-1 infection, as documented by a rapid HIV test or any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than rapid HIV and ELISA is acceptable as an alternative confirmatory test.

3. Antiretroviral therapy naive (defined as no previous ART except if used for pre- or post-exposure prophylaxis or women who were administered ART for prevention of mother to child transmission; in all cases, therapy cannot exceed 12 weeks, and there can be no ART in the last 90 days).

4. Plasma HIV-1 RNA > 5,000 copies/mL within 30 days before Entry (Day 1) by any FDA-approved test for quantifying HIV-1 RNA at any certified laboratory.

5. CD4+ count > 350 cells/mm3 within 30 days before Entry (Day 1).

6. For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of < 25 miU/mL at Screening (baseline) and Day 1.
Females of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation),
Subjects who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, salpingotomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives. Acceptable documentation of sterilization and menopause is the woman’s self-reported history of surgical sterilization, menopause or male partner’s asoospermia. Follicle stimulating hormone-release factor (FSH) measurement can be used to document menopausal range.

7. All subjects must agree not to participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). If participating in sexual activity that could lead to pregnancy, the subject must agree to use two reliable methods of contraception while receiving study treatment and for 6 weeks after stopping study treatment.
Two of the following methods must be used concomitantly :
Condoms (male or female) with or without a spermicidal agent
Diaphragm or cervical cap with spermicide
Intrauterine device (IUD)
Hormonal-based contraception.

8. Adequate venous access in the left or right arm to allow collection of a number of blood samples.

9. Provide written informed consent to participate in the study and be willing to comply with the study procedures.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently has any active AIDS defining illness ( according to the CDC Surveillance Case Definition for HIV Infection, AIDS-Defining Conditions, updated December 5, 2008.

2. Patients who are expected to need systemic antiviral therapy at any time during their participation in the study.

3. Patients who have received an investigational drug for HIV, HIV vaccine, immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or other investigational therapy within 30 days prior to study entry.

4. Acute or chronic viral hepatitis as defined by the presence of: 1) anti-HAV IgM Ab (acute hepatitis A), 2) HCV Ab with a detectable HCV RNA by PCR (acute or chronic hepatitis C) or 3) hepatitis B surface antigen or HBV DNA in subjects with isolated HBcAb, defined as negative HBsAg, negative HBsAb and positive HBcAb (acute or chronic hepatitis B).

5. History or other evidence of renal disease.

6. Abnormal hematological and biochemical parameters within 30 days of Entry (Day 1):
a. Absolute neutrophil count <1000/mm3
b. Haemoglobin <12 g/L in females or <13 g/L in males
c. Platelet count <75,000/mm3
d. Estimated creatinine clearance < 60 mL/minute. Value will be calculated using the Cockcroft-Gault formula.
e. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase >/= 2.5 times upper limit of normal.

7. Screening ECG QTc value >/= 450 ms.

8. Consumption / administration of prohibited concomitant medication (prescribed, over-the-counter or complementary). This list is not exhaustive and any medication taken from 30 days prior to first dose through to the end of the participation in the study must be permitted by the Biotron Medical Monitor in consultation with the Investigator.

9. Active alcohol and/or drug abuse that, in the opinion of the site investigator, would interfere with adherence to study requirements.

10. Positive results on urine screen for drugs of abuse (excluding THC) at Screening or Day 1.

11. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent non-steroidal anti-inflammatory medications for management, etc).

12. History of documented or presumed coronary artery disease or cardiovascular disease, or clinically significant arrhythmia.

13. History of a severe seizure disorder or current anticonvulsant use.

14. Evidence of an active or suspected cancer or a history of malignancy within 2 years.

15. History of having received any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.

16. History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations, with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease.

17. Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

18. Known allergy/sensitivity to any components of study drug or its formulation.

19. Current habit of smoking and unable to refrain from smoking during the confinement periods in this trial.

20. Difficulty abstaining from grapefruit, star fruit, including grapefruit and star fruit containing products from 7 days prior to the first dose of investigational product until the end of the dosing period.

21. Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to anticipated dose administration.

22. Current use of herbal medications or unwillingness to cease use during study participation.

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)
Patients will be assigned to a sequentially numbered treatment in accordance with the randomisation schedule following confirmation of eligibility on day 1. An unblinded pharmacist at the site will dispense the study medication to the blinded site staff according to the randomisation schedule. The dispensed medication will carry the participant's unique study number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
3 block randomisation algorithm
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Allocation of treatment is in a ratio of 2:1, BIT225 to placebo
Phase
Phase 1
Type of endpoint(s)
Safety
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
Current
Final
Recruitment outside Australia
Country [1] 4380 0
Thailand
State/province [1] 4380 0

Funding & Sponsors
Funding source category [1] 285530 0
Commercial sector/Industry
Name [1] 285530 0
Biotron Limited
Address [1] 285530 0
Suite 1.09
56 Delhi Rd
North Ryde NSW 2113
Country [1] 285530 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Biotron Limited
Address
Suite 1.09
56 Delhi Rd
North Ryde NSW 2113
Country
Australia
Secondary sponsor category [1] 284372 0
None
Name [1] 284372 0
Address [1] 284372 0
Country [1] 284372 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287559 0
Siriraj Institutional Review Board, Faculty of Medicine, Mahidol University
Ethics committee address [1] 287559 0
2 Prannok Road. Bangkoknoi. Bangkok 10700
Ethics committee country [1] 287559 0
Thailand
Date submitted for ethics approval [1] 287559 0
16/06/2011
Approval date [1] 287559 0
18/08/2011
Ethics approval number [1] 287559 0
00005261

Summary
Brief summary
Biotron is developing a novel inhibitor of HIV-1, called BIT225. This early phase trial will assess the safety of BIT225 in patients with HIV-1 infection who have not received any other therapy for HIV-1. It will also assess how well BIT225 is tolerated, the level of BIT225 in the blood following oral administration, and how well BIT225 performs at reducing HIV-1 levels in the blood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34372 0
A/Prof Winai Ratanasuwan
Address 34372 0
Department of Preventative and Social Medicine
Siriraj Hospital
Bangkok 10700
Country 34372 0
Thailand
Phone 34372 0
+66 2 419 7284
Fax 34372 0
Email 34372 0
winai.rat@mahidol.ac.th
Contact person for public queries
Name 17619 0
Dr Michelle Miller, PhD
Address 17619 0
Biotron Limited
Suite 1.09
56 Delhi Rd
North Ryde NSW 2113
Country 17619 0
Australia
Phone 17619 0
+61 2 9805 0488
Fax 17619 0
+61 2 9805 0688
Email 17619 0
mmiller@biotron.com.au
Contact person for scientific queries
Name 8547 0
Dr Michelle Miller, PhD
Address 8547 0
Biotron Limited
Suite 1.09
56 Delhi Rd
North Ryde NSW 2113
Country 8547 0
Australia
Phone 8547 0
+61 2 9805 0488
Fax 8547 0
+61 2 9805 0688
Email 8547 0
mmiller@biotron.com.au