Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001475437
Ethics application status
Approved
Date submitted
2/06/2015
Date registered
24/10/2016
Date last updated
17/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Ala Wai Phase 1 safety and tolerability study with 14 healthy participants
Scientific title
An Healthy Volunteer, Open-Label, Cross-Over Phase I Study to Determine the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose of AWP-09VDB-S under Fed and Fasted Conditions
Secondary ID [1] 286843 0
None
Universal Trial Number (UTN)
U1111-1170-9013
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
the treatment and prophylaxis of influenza 295237 0
Condition category
Condition code
Infection 295482 295482 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
New formulation of zanamivir, AWP-09VDB-S, to be administered in a gastric resistant capsule.
Participants will receive two doses in total. Each dose is 2 x capsules of 150mg (300mg total) in feed and fasted state. 4-13 days washout between period 1 and 2
Compliance check of the mouth and hand at administration.

FED Cohort: Participants in the fed period will be dosed following a high–fat, high-calorie breakfast. These participants will be required to fast overnight for at least 10 hours until 30 minutes prior to their scheduled dosing times, when they will be given a standard high-fat, high calorie breakfast which will be entirely consumed within 30 minutes. The breakfast will consist of two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes (1 serving or approximately 114 gm) and 240 mL of whole milk. Participants will fast for at least 4 hours following dosing. IP will be administered with 240 mil of water. No food is allowed for at least 4 hours post-dose. Water can be consumed as desired except for one hour after drug administration.
FASTED Cohort Participants : Following an overnight fast of at least 10 hours, participants will be administered IP with 240 mL of water. No food is allowed for at least 4 hours post-dose. Water can be consumed as desired except for one hour before and after drug administration.
Intervention code [1] 292008 0
Treatment: Drugs
Comparator / control treatment
This study will examine the safety, tolerability and pharmacokinetics of a single dose of the investigational product AWP-09VDB-S, under FED and FASTED conditions.

The participants will be randomised in a 1:1 ratio to receive the AWP-09VDB-S in either the FED or FASTED state in period 1.

After a washout period of 4-13 days of AWP-09VDB-S administration in Period 1, eligible participants will return for Period 2 and will cross over to receive the AWP-09VDB-S in the opposite state (FED or FASTED) to which they were randomised in Period 1.
Control group
Active

Outcomes
Primary outcome [1] 295208 0
Safety Assessments: This study assesses the safety and tolerability of AWP-09VDB-S under FED and FASTING conditions. Safety will be determined by evaluating physical examinations, ECGs, vital signs, clinical laboratory parameters, and AEs. If deemed necessary, additional safety measurements will be performed at the discretion of the PI and/or Sponsor.
Timepoint [1] 295208 0
A follow-up safety evaluation will be performed 7(+/-2) days after each dose. This may be done at the start of Period 2 if less than 9 days has elapsed
Secondary outcome [1] 315065 0
To assess the pharmacokinetics (PK) of a single oral dose of AWP-09VDB-S when administered to healthy volunteers in the presence and absence of food. Pharmacokinetic profiles: Cmax, Tmax, AUClast, AUC0-inf, Kel, t1/2 and CL/F computed from plasma zanamivir concentrations and Ae(t’-t’’), Ae0-24, Re, Rmax, and TRmax computed from the individual urine zanamivir concentrations.
Urine PK smaples will be collected and refrigerated during the collection intervals. At the end of each interval, total urine volume will be measured, and an aliquot will be collected and stored frozen for PK analysis if deemed necessary by Ala Wai Pharma.
Timepoint [1] 315065 0
PK blood sample (0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8 and12 hours after dosing).
PK urine collection (during collection interval times of 0- 4, 4- 8, 8- 12 and 12-24 hours after dosing).

Eligibility
Key inclusion criteria
1. Adult male and/or female healthy volunteers with a minimum age of at least 18 years and maximum age of 65 years at the time of screening.
2. Medically healthy with clinically insignificant screening results (e.g. laboratory profiles, medical history, ECGs, physical exam) as judged by the PI.
3. Negative urine drug screen /alcohol breath test prior to Day -1.
4. Availability of participant for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed, Informed Consent Form.
5. If male, agrees to be sexually abstinent or to use a condom (with the female sexual partner also to use an effective method of contraception) when engaging in sexual activity from admission through completion of the end-of study. Participants will be advised to use a condom (with the female sexual partner also to use an effective method of contraception) for 30 days following the last administration of the investigational product, and to not donate sperm during this same period of time.
6. Females of childbearing potential must either be sexually inactive (abstinent) for 14 days prior to the first administration of the investigational product and remain so through 30 days following the final dosing of the investigational product, or have been using one of the following acceptable methods of birth control for the times specified:
a. Intra-uterine device (IUD) in place for at least 3 months prior to the first administration of the investigational product.
b. Double barrier method (e.g., condom and diaphragm) for at least 14 days prior to the first administration of investigational product.
c. Male partner who is surgical sterile (vasectomy) at least 6 months prior to the first administration of investigational product and is the sole sexual partner for that female participant.
d. Adequate hormonal contraception.

Female participants who claim to be sexually inactive, but become sexually active during the course of the study must agree to use a double barrier method (e.g., condom and diaphragm) from the time of the start of sexual activity through 30 days following the final dosing.
In addition, female participants of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 30 days following the final dosing of the investigational product.

7. Females of non-childbearing potential have undergone one of the following sterilization procedures at least 6 months prior to the first investigational product administration:
a. Sterilization (with a copy of the confirmation test) and be using a barrier method (condom or diaphragm) throughout the study;
b. bilateral tubal ligation with a barrier method (condom or diaphragm) throughout the study;
c. hysterectomy;
d. bilateral oophorectomy;

or be postmenopausal with amenorrhea for at least 1 year prior to the first administration of the investigational product and follicle stimulating hormone (FSH) serum levels. FSH serum levels less than or equal to 20 IU/L.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. History of confirmed chronic and/or serious pulmonary disease, including asthma or chronic obstructive pulmonary disease (COPD).
2. Known or suspected history of hypersensitivity to any components of the investigational product – zanamivir, glycerol or diglycerides.
3. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
4. Presence or history of clinically significant lung infection
5.Presence or history of influenza within the past three weeks.
6. Participants who meet the following criteria at baseline:
a. ALT or AST greater than or equal to 3xULN and bilirubin greater than or equal to 2xULN, or
b. ALT greater than or equal to 5xULN.
7. Participating in a clinical trial with an investigational drug within 30 days preceding this trial.
8. Blood donation within 45 days preceding this trial.
9. Participants who are known to have serum hepatitis or who are carriers of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody or have a positive result to the test for Human Immunodeficiency Virus (HIV).
10. Use of zanamivir (Relenza Registered Trademark) within 4 days preceding confinement for either dose period.
Presence or history of clinically significant lung infection

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)
Following confirmation of eligibility (either Day -1 or Day 1 prior to IP administration), participants will be assigned a unique Randomisation Number, and will be randomised in a 1:1 ratio for Period 1 to either the FED or FASTED group in accordance with the randomisation schedule. Each participant will then cross over to the other group (FED or FASTED) in Period 2. Allocation is not concealed.

After a washout period of 4-13 days of AWP-09VDB-S administration in Period 1, eligible participants will return for Period 2 and will cross over to receive the AWP-09VDB-S in the opposite state (FED or FASTED) to which they were randomised in Period 1.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The generation of the Randomisation List will be performed by using a computer randomisation system.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
14 volunteers are needed. As this is an exploratory Phase I safety and tolerability study, no formal sample size has been calculated. However, the sample size chosen is considered adequate to meet the study objectives.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
18/10/2016
Date of last participant enrolment
Anticipated
31/10/2016
Actual
31/10/2016
Date of last data collection
Anticipated
Actual
2/01/2017
Sample size
Target
14
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 3860 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 9757 0
4000 - Brisbane

Funding & Sponsors
Funding source category [1] 291396 0
Commercial sector/Industry
Name [1] 291396 0
Ala Wai Australia Pty Ltd
Country [1] 291396 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services Pty Ltd
Address
Level 4, 88 Jephson St, TOOWONG QLD 4066, Australia
Country
Australia
Secondary sponsor category [1] 290071 0
Commercial sector/Industry
Name [1] 290071 0
Ala Wai Pharma, Inc.
Address [1] 290071 0
4471 Kahala Ave,
Honolulu, Hawaii, 96816, USA
Country [1] 290071 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292946 0
Bellberry-HREC
Ethics committee address [1] 292946 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 292946 0
Australia
Date submitted for ethics approval [1] 292946 0
Approval date [1] 292946 0
15/07/2016
Ethics approval number [1] 292946 0

Summary
Brief summary
An Healthy Volunteer, Open-Label, Cross-Over Phase I Study to Determine the Safety, Tolerability and Pharmacokinetics of a Single Oral Dose of AWP-09VDB-S under Fed and Fasted Conditions. AWP-09VDB-S is a novel formulation of zanamivir, neuraminidase inhibitor used for the treatment and prophylaxis of influenza, and the permeability enhancers glycerol and Capmul MCM C8 presented in a gastric resistant capsule.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 57766 0
Dr Paul Griffin
Address 57766 0
Dr Griffin Manager of Medical Services at Q-Pharm.
Level 5 (Clinic and Recruitment & Outpatients)
Clive Berghofer Cancer Research Centre (CBCRC)
300C Herston Road
Herston
QLD 4006
Country 57766 0
Australia
Phone 57766 0
+61 7 3845 3620
Fax 57766 0
Email 57766 0
[email protected]
Contact person for public queries
Name 57767 0
Dr Gregor Rozenberg
Address 57767 0
Dr Gregor Rozenberg
Ala Wai Australia Pty Ltd
17 Praeger Street
Chapel Hill, QLD 4069
Country 57767 0
Australia
Phone 57767 0
+61 412 911 404
Fax 57767 0
Email 57767 0
[email protected]
Contact person for scientific queries
Name 57768 0
Dr Paul Griffin
Address 57768 0
Dr Griffin Manager of Medical Services at Q-Pharm.
Level 5 (Clinic and Recruitment & Outpatients)
Clive Berghofer Cancer Research Centre (CBCRC)
300C Herston Road
Herston
QLD 4006
Country 57768 0
Australia
Phone 57768 0
+61 7 3845 3620
Fax 57768 0
Email 57768 0
[email protected]

No information has been provided regarding IPD availability


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.