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Trial registered on ANZCTR


Registration number
ACTRN12623000821695
Ethics application status
Approved
Date submitted
20/06/2023
Date registered
1/08/2023
Date last updated
9/05/2024
Date data sharing statement initially provided
1/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Single-center, 2-arm Interventional Study to Determine the Association between the Gut Microbiome and the Pharmacokinetic Profile of Palbociclib in Healthy Female Volunteers.
Scientific title
A Single-center, 2-arm Interventional Study to Determine the Association between the Gut Microbiome and the Pharmacokinetic Profile of Palbociclib in Healthy Female Volunteers
Secondary ID [1] 309559 0
BIOMAP-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 329849 0
Condition category
Condition code
Cancer 326757 326757 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open label, single-centre, interventional study investigating the associate between the gut microbiome and pharmacokinetic PK profile of Palbociclib administered as a single oral dose in healthy adult volunteers.

Treatment will comprise of 10 healthy female volunteers between the ages of 18 - 65. Male participants have been excluded from the study to control for sex differences in the microbiome of breast cancer patients [Kim et al, 2020]. Participants will receive a single oral dose of palbociclib (125 mg).

The expected total study duration for each participant will be up to 36 days which includes a 28-day screening period, 1-day dosing period and 6-day follow up period.

Participants identified by an online pre-screen will be required to attend the clinical facility on any day between Day -28 and Day -5 to provide informed consent and further eligibility assessment. Eligible participants will be provided with two stool sample kits and a food frequency questionnaire. A stool sample must be collected by participants within 3 days of presenting to the clinical facility on Day -1. Following provision of the stool sample, participants will be admitted to the clinical facility on Day -1 for confirmation of eligibility prior to receiving a single dose of study drug on Day 1. Participants will be confined to the clinical facility for a further 2 days post-dose to allow for 24-hour PK sampling and 48-hour clinical observation prior to discharge on Day 3. A second stool sample will need to be provided by participants within 3 days post dose. Participants will be required to attend the clinical facility for final safety assessments at the end of study (EoS) visit on Day 7.

One member of the study team will be responsible for study drug administration and verified by a second member of staff.

Adherence to Intervention will be managed via recording in appropriate drug accountability records
Intervention code [1] 325982 0
Treatment: Drugs
Comparator / control treatment
No Control Group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334618 0
To determine the pharmacokinetics of palbociclib.

The Pharmacokinetic parameters include:
o Drug plasma concentration (ng/mL)
o Time of plasma collection post-drug administration
o Drug peak plasma concentration (Cmax)
o Time taken to reach maximum serum drug concentration (tmax)
o Drug terminal half-life for absorption (t1/2a)
o Drug terminal half-life for elimination (t1/2e)
o Drug area under the concentration-time curve from time 0 to time t (AUC0-t)
o Drug area under the concentration-time curve from time 0 to the last measurable concentration (AUClast)
o Area under the drug concentration-time curve from time zero infinity (AUCinf)
Timepoint [1] 334618 0
Blood plasma samples will be collected within 1 hr pre-dose on Day 1 then at 0.5 hr, 1hr, 2hrs, 4 hrs, 6 hrs,8hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose.
Primary outcome [2] 335458 0
To analyse the gut microbiome profile of palbociclib
Timepoint [2] 335458 0
Participants will be required to provide a baseline stool sample within 3 days prior to dosing with study drug on Day 1 and a second stool sample between 1 and 4 days after dosing (Day 2 to Day 5) for microbiome analysis.
Secondary outcome [1] 421434 0
To assess the safety and tolerability of palbociclib following a single dose.

Endpoints include:
• Incidence, severity and relationship of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation of study treatment.
• Changes from baseline in:
Vital signs measurements (pulse rate [PR], systolic and diastolic blood pressure [BP], tympanic temperature, respiratory rate [RR]).
Clinical laboratory results (haematology, serum chemistry, urinalysis)
ECG parameters
Timepoint [1] 421434 0
AE's and SAE's will be graded using the most current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5-point scale assessed daily and as required from Screening to Day 7 post-dose/End of Study (EoS) visit.

Vital signs will be measured via the following methods - pulse rate (oximeter), blood pressure (sphygmomanometer), tympanic temperature (digital thermometer), respiratory rate (manual breath count) and assessed from Screening, Day -1, 1 hr pre-dose Day 1 then 15 minutes, 30 minutes, 1 hour and 4 hours post-dose, Day 2 24 hrs post-dose +/- 2 hrs, Day 3 48 hrs post-dose, Day 7 post-dose/EoS visit.

ECGs will be performed in triplicated and assessed from Screening, Day -1, 1 hr pre-dose Day 1 and 4 hours post-dose, Day 2 24 hrs post-dose +/- 2 hrs, Day 3 48 hrs post-dose, Day 7 post-dose/EoS visit.

Safety laboratory blood samples (haematology, serum chemistry and urinalysis) will be assessed at Screening, Day -1, Day 2 24 hrs post-dose and Day 7 post-dose/EoS visit.

Eligibility
Key inclusion criteria
1. Must have given written informed consent, before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Healthy female, aged between 18 and 65 years, inclusive at screening.
3. Body mass index (BMI) of 18 to 32 kg/m2, inclusive.
4. Participant is medically healthy (in the opinion of the PI), as determined by pre-study medical history and without clinically significant abnormalities including:
a. Physical examination without any additional clinically relevant findings
b. Systolic blood pressure in the range of 90 to 140 mmHg and diastolic blood pressure in the range of 40 to 90 mmHg after 5 minutes in supine position.
c. Heart rate in the range of 40 to 100 beats/minute after 5 minutes rest in supine position.
d. Body temperature (tympanic), between 35.5°C and 37.7°C.
e. Electrocardiogram (ECG) without clinically significant abnormal including QT interval corrected for Fredericia (QTcF) between 350 to 470 msec.
Note: The above assessments may be repeated, if abnormal values were recorded in the first instance, at the discretion of the Investigator (or delegate).
5. Participant is willing to refrain from consuming food or beverages containing caffeine and/or xanthene products, within 24 hours prior to check-in on Day -1.
6. Participants must be of non-child-bearing potential i.e., surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or, if of child-bearing potential:
a. Must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test on Day -1.
b. Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 1 month after the last dose of study drug.
c. If not exclusively in a same-sex relationship, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to dose administration until at least 1 month after the last dose of study drug.
Women who have been surgically sterilised through tubal ligation are permitted to participate, if they agree to use an additional barrier method of contraception from one month prior to the first dose of study drug, until at least 1 month after the last dose of study drug.
7. Willing and able to comply with all scheduled visits, treatment plans, laboratory tests and other study procedures.
8. Willing and able to perform pre-dose and post-dose stool sample collection within the designated timeframe
9. Agreement to have their anonymized data stored in the cloud for up to 15 years after the conclusion of the study.
10. Agreement to have anonymised data incorporated into the BioCorteX proprietary platform for future predictive purposes.

Minimum age
18 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Hypersensitivity or other clinically significant reaction to the study drug or its active ingredients.
2. History of any clinically significant disorder, including cardiovascular, hematologic, pulmonary, hepatic, renal, gastrointestinal, connective tissue disease, uncontrolled endocrine/metabolic, oncologic (within the last 5 years), neurologic, and psychiatric diseases, or any disorder that may prevent the successful completion of the study or influence the absorption, distribution, metabolism, excretion, or action of the study drug. Participants with fully resolved childhood asthma with no adult reoccurrence and participants who have undergone cholecystectomy may be included at the discretion of the PI.
3. Absolute neutrophil count <2000 /mm3
4. Platelet count < 150,000 /mm3
5. Antibiotic usage with 30 days prior to screening
6. Concurrent enrolment in another clinical study, or dosed in another clinical study within 30 days or 5 half-lives (whichever is longer) prior to screening.
7. Regular consumption of >14 standard alcoholic drinks/week where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], 30 mL spirit [40% Alc/Vol]).
8. Positive alcohol breath or urine test at Screening or upon admission to the clinic on Day -1.
9. Positive urine drugs of abuse test at Screening or upon admission to the clinic on Day -1.
10. Use of tobacco products or nicotine-containing products (including smoking cessation aids such as gum or patches), within 30 days prior to screening, and/or a positive urine cotinine test at Screening or upon admission to the clinic on Day -1.
11. Participant is breastfeeding, or pregnant, or planning to breastfeed or become pregnant during the study.
12. Known substance abuse or medical, psychological, or social conditions that, in the opinion of the PI (or delegate), may interfere with the participants inclusion in the clinical study or evaluation of the clinical study results.
13. Use of any prescription or over-the-counter medication (including herbal products, diet aids, probiotics and hormone supplements) within 30 days or 5 half-lives of the medication (whichever is longer) prior to dosing with study drug and throughout the study period, with the exception of hormonal contraceptives.
14. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
15. Participant has donated blood or blood products within 30 days prior to screening.
16. Any other condition or prior therapy that in the opinion of the Investigator (or delegate) would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
17. Unable to provide pre-dose stool sample between Day -3 and predose on Day 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
In keeping with previous PK studies, a sample size of 20 participants was selected for this study. BioCorteX engine analysis was employed to calculate this sample size.

Exploratory outcomes analysis will be used to determine;
- any individual factors within the stool microbiome that are associated with pharmacokinetic differences between participants.
- any factors within participant demographic data that are associated with pharmacokinetic differences between participants.
- if any biochemistry or haematology blood results (full blood count, renal and liver profile) taken at baseline are associated with pharmacokinetic differences between participants.
- if study drug has effects on the microbiome.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/08/2023
Actual
31/07/2023
Date of last participant enrolment
Anticipated
Actual
3/09/2023
Date of last data collection
Anticipated
Actual
3/09/2023
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 24652 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 40263 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 313750 0
Commercial sector/Industry
Name [1] 313750 0
BioCorteX Pty Ltd
Country [1] 313750 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
BioCorteX Pty Ltd
Address
Level 5
63 Pirie Street
Adelaide, South Australia 5000
Country
Australia
Secondary sponsor category [1] 315568 0
Commercial sector/Industry
Name [1] 315568 0
Avance Clinical Pty Ltd
Address [1] 315568 0
213 Glynburn Rd,
Firle, South Australia 5070
Country [1] 315568 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312921 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [1] 312921 0
Ethics committee country [1] 312921 0
Australia
Date submitted for ethics approval [1] 312921 0
31/05/2023
Approval date [1] 312921 0
21/07/2023
Ethics approval number [1] 312921 0
2023-05-599

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126342 0
Dr Kristi McLendon
Address 126342 0
Q-Pharm Pty Ltd
Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006
Country 126342 0
Australia
Phone 126342 0
+61 07 3707 2720
Fax 126342 0
Email 126342 0
[email protected]
Contact person for public queries
Name 126343 0
Kristi McLendon
Address 126343 0
Q-Pharm Pty Ltd
Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006
Country 126343 0
Australia
Phone 126343 0
+61 07 3707 2720
Fax 126343 0
Email 126343 0
[email protected]
Contact person for scientific queries
Name 126344 0
Kristi McLendon
Address 126344 0
Q-Pharm Pty Ltd
Level 5 Clive Berghofer Cancer Centre Research Centre,
300 Herston Road, Herston, QLD 4006
Country 126344 0
Australia
Phone 126344 0
+61 07 3707 2720
Fax 126344 0
Email 126344 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Intellectual and property considerations


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.