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Trial registered on ANZCTR


Registration number
ACTRN12619001577101
Ethics application status
Approved
Date submitted
4/11/2019
Date registered
15/11/2019
Date last updated
25/02/2020
Date data sharing statement initially provided
15/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Dapagliflozin Extended Release Capsules in Healthy Volunteers.
Scientific title
An Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Dapagliflozin Extended Release Capsules in Healthy Volunteers.
Secondary ID [1] 299692 0
LYN-045-C-001
Secondary ID [2] 299693 0
CM5619
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 315046 0
Condition category
Condition code
Metabolic and Endocrine 313376 313376 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is LYN-045, an extended release (ER) oral capsule containing dapagliflozin 35 mg. The rationale for the development of this ER formulation is to reduce the frequency of dosing orally administered dapagliflozin once weekly or less and thereby improving the management of type 2 diabetes.
The study will consist of three cohorts, with each cohort receiving a different formulation of LYN-045.
In Cohort 1, 8 participants will receive the base formulation - LYN-045-B.
Each participant will receive:
On day 1, a single dose of immediate release (IR) dapagliflozin (FORXIGA®) 10 mg oral tablet that will be administered to facilitate characterisation of the dapagliflozin pharmacokinetics.
On day 4, the LYN-045-B will be administered as single dose ER oral capsule containing 35 mg dapagliflozin. On both days (1 and 4), the single oral dose of the IR dapagliflozin tablet or LYN-045-B ER oral capsule will be administered and directly observed by a trained nurse (at a minimum) in an inpatient unit.
Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 4 weeks, from the time of enrolment through the last study visit.
In Cohort 2, 16 participants will be dosed with the stiffer core formulation – LYN-045-SC – 8 with a stabilising ring and 8 without.
In Cohort 3, 16 participants will be dosed with the flexible arm formulation – LYN-045-FA – 8 with a stabilising ring and 8 without.
Each participant in Cohort 2 and 3 will receive:
On day 1, the LYN-045-SC will be administered as single dose ER oral capsule containing 35 mg dapagliflozin. The single oral dose of LYN-045-SC or LYN-045-FA ER oral capsule will be administered and directly observed by a trained nurse (at a minimum) in an inpatient unit.
Eligible healthy volunteers enrolled into the study should expect to participate in the study for up to 4 weeks, from the time of enrolment through the last study visit.
Intervention code [1] 315958 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321857 0
Safety and tolerability of LYN-045-B, LYN-045-SC and LYN-045-FA, when administered as a single dose, assessed from adverse events (AEs).
Timepoint [1] 321857 0
Adverse events will be collected at screening visit, upon admission to the inpatient unit (day minus 1), and at dosing of IR dapagliflozin and the three days that follow (C1 only)). They will also be assessed upon dosing of LYN-045 at 0, 4, 6 and 12 hours post dose and daily on inpatient days as well as outpatient days. Adverse events will be assessed by physical exam, electrocardiogram, vital signs, safety labs (serum assay), urine dipstick and participant self-report. Directed physical exams will be performed on screening visit, upon admission to the inpatient unit and prior to dosing with LYN-045, upon discharge from the inpatient unit and on outpatient visit days. Vital signs will be collected screening visit, upon admission to the inpatient unit (day minus 1) at dosing of IR dapagliflozin and the three days that follow (C1 only). Upon dosing of LYN-045 at 0, 4 and 12 hours post dose, and daily on inpatient days and Outpatient days. Safety labs will be collected at screening visit, at dosing of IR dapagliflozin (Cohort 1 only), dosing of LYN-045 and at study day 10 (c1) or Day 7 (C2 and 3) by serum assay. Electrocardiograms will be performed at screening visit, upon admission to the inpatient unit (day minus 1), at dosing of LYN-045 (pre-dose and 4 hours post dose) and at days 7 and 10 (C1) or days 4 and 7 (C2 and 3).
Primary outcome [2] 321858 0
Pharmacokinetics of dapagliflozin following administration of LYN-045-B, LYN-045-SC or LYN-045-FA as a single dose, as assessed by: e.g. Cmax, Cmin, Tmax, Tlast, Kel, AUC0-24, AUC0-t, AUC0-168, and AUC0-8 by validated serum assay.
Timepoint [2] 321858 0
IR dapagliflozin PK sampling (C1 only) at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 8, and 12 hours post-dose Day 1 through Day 4 at 24, 36, 48, 60, and 72 hours post-dose by validated serum assay. LYN-045 PK sampling at 0 hours (pre-dose; also 72-hour IR post-dose timepoint (C1 only)), 1, 2, 4, 6, 8, and 12 hours on Day 4 (C1) or D1 (C2 and 3) and twice-daily through to the morning of Day 11 (C1) or D8 (C2 and 3) (e.g. 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 hours post-dose) by validated serum assay.
Secondary outcome [1] 376496 0
Gastrointestinal transit of LYN-045 capsules by imaging assessments (MRI or X ray).
Timepoint [1] 376496 0
MRI will be performed two days post dosing of LYN-045, 4 days post dosing of LYN-045 and 7 days post dosing of LYN-045/discharge from inpatient unit in each cohort., Abdominal x-rays will be performed on days 15 and 18 (C1) or Days 12 and 15 C2 and 3) (outpatient visits).

Eligibility
Key inclusion criteria
1. Provision of signed and dated informed consent;
2. Stated willingness to comply with all protocol-specified procedures and availability for the duration of the study;
3. Good current health, in the opinion of the Investigator, as evidenced on review of medical history, no significant gastrointestinal abnormalities, physical examination, concomitant medications, and other safety assessments;
4. Body mass index (BMI) of greater than or equal to 18 kg/m2 and less than or equal to 30 kg/m2;
5. Body weight greater than or equal to 55 kg.

Minimum age
18 Years
Maximum age
49 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any known clinically significant esophageal or gastrointestinal disease;
2. Unusual score for swallowing questionnaire.
3. Do not demonstrate normal swallowing and gastrointestinal passage for capsule, as assessed while undergoing imaging studies.
4. Symptoms suggestive of irritable bowel syndrome, functional constipation or functional diarrhea;
5. History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs;
6. Clinically significant abnormal safety (e.g., physical examination) or safety laboratory assessments;
7. Hepatitis B, hepatitis C, or H. pylori infection at Screening, unless there is a confirmed medical history of successful treatment;
8. Use of prescription medications, natural remedies, vitamins or non-prescription medicines associated with changes to gastric motility or pH or management of gastrointestinal symptoms within two weeks of study dosing;
9. Individuals who are contraindicated based on dapagliflozin;
10. History of any drug or alcohol use disorder in the past 2 years;
11. Individuals of reproductive potential who are (hetero) sexually active but unwilling to use acceptable means of contraception through the End of Study;
12. Individuals who are nursing or who have positive or indeterminate pregnancy tests at screening.



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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
SA
Recruitment hospital [1] 15086 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 28382 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 304169 0
Commercial sector/Industry
Name [1] 304169 0
Lyndra Australia Pty Ltd
Address [1] 304169 0
Level 13 41 Exhibition Street
Melbourne VIC 3000
Country [1] 304169 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lyndra Australia Pty Ltd
Address
Level 13 41 Exhibition Street
Melbourne VIC 3000
Country
Australia
Secondary sponsor category [1] 304397 0
None
Name [1] 304397 0
Address [1] 304397 0
Country [1] 304397 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304643 0
Bellberry Limited HREC Committee D
Ethics committee address [1] 304643 0
123 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 304643 0
Australia
Date submitted for ethics approval [1] 304643 0
02/10/2019
Approval date [1] 304643 0
28/10/2019
Ethics approval number [1] 304643 0
2019-09-755

Summary
Brief summary
An open-label study in healthy volunteers:
To evaluate the safety, tolerability and pharmacokinetics of dapagliflozin (35 mg) extended release capsules (LYN-045) in healthy volunteers

To characterize the pharmacokinetics (PK) of dapagliflozin (35 mg) extended release capsules (LYN-045).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97698 0
Prof Sepehr Shakib
Address 97698 0
CMAX
Level 5
18a North Terrace
Adelaide SA 5000
Country 97698 0
Australia
Phone 97698 0
+61 0870742823
Fax 97698 0
Email 97698 0
sepehr.shakib@sa.gov.au
Contact person for public queries
Name 97699 0
Ms Jessica Ballinger
Address 97699 0
(Director)
Lyndra Australia Pty Ltd
Level 13
41 Exhibition Street
Melbourne VIC 3000
Country 97699 0
Australia
Phone 97699 0
+1 857 201 5322
Fax 97699 0
Email 97699 0
jballinger@lyndra.com
Contact person for scientific queries
Name 97700 0
Dr Bernard Silverman
Address 97700 0
Lyndra Therapeutics Inc
65 Grove Street
Suite 301
Watertown, MA 02472
Country 97700 0
United States of America
Phone 97700 0
+1 617 803 2445
Fax 97700 0
Email 97700 0
bsilverman@lyndra.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data underlying published results only
When will data be available (start and end dates)?
3 moths following publication, 4 years following publication
Available to whom?
case by case basis at the discretion of Lyndra (primary sponsor)
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Required to sign data access agreement by emailing primary sponsor (jdube@lyndra.com).
What supporting documents are/will be available?
No other documents available
Summary results
No Results