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Trial registered on ANZCTR


Registration number
ACTRN12618001988246
Ethics application status
Approved
Date submitted
29/11/2018
Date registered
12/12/2018
Date last updated
21/01/2019
Date data sharing statement initially provided
12/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Double-Blind, Randomized, Placebo-Controlled Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of CT-868 in Healthy Overweight/Obese Participants and in Patients with
Type 2 Diabetes Mellitus
Scientific title
A Double-Blind, Randomized, Placebo-Controlled Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of CT-868 in Healthy Overweight/Obese Participants and in Patients with
Type 2 Diabetes Mellitus
Secondary ID [1] 296678 0
Nil known
Universal Trial Number (UTN)
U1111-1224-4463
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obese 310522 0
Type 2 Diabetes Mellitus 310523 0
Condition category
Condition code
Diet and Nutrition 309234 309234 0 0
Obesity
Metabolic and Endocrine 309235 309235 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single ascending dose cohorts (Part 1)
Planned doses of CT-868: 0.1mg, 0.5mg, 1.5mg, 3.0mg, 4.5 mg, 5.75mg given by subcutaneous (SC) injection. Injection given by staff in the study unit.
Multiple ascending dose cohorts (Part 2)
Planned doses of CT-868: 0.5mg, 1.5mg, 3.0mg, 4.5 mg, final dose to be determined by dose escalation committee based on preceding safety and PK data. SC injection given once daily for 14 days. For all study participants, the appropriate volume of CT-868 IP or matched placebo will be administered as a SC injection into/under the skin of the abdominal region. For the multiple–dose cohorts (Part 2 and Part 3), injection sites on the abdomen will be rotated to prevent ISRs. Injection given by staff in the study unit.
Multiple dose in Type 2 diabetes (T2DM) (Part 3)
Planned dose of CT-868: dose to be determined by dose escalation committee based on preceding safety and PK data. SC injection given once daily for 28 days
Injection given by staff in the study unit on Days 1-5 and during this time, participants will be trained to self-administer the SC injection. Participants will return to the study unit every 3 days from Day 5 and the SC injection will be given by study site staff on those days. Participants will then self-administer the SC injection using a pre-filled syringe on the days not required to visit the site. They will have a diary to complete to document study drug administration.
Participants may only take part in one cohort for the study
Intervention code [1] 312991 0
Treatment: Drugs
Comparator / control treatment
Placebo for SC injection will be normal saline and will be administered in a total volume to match the doses for the intervention treatment
Control group
Placebo

Outcomes
Primary outcome [1] 308201 0
Safety and tolerability will be assessed by reporting of adverse events, clinical laboratory tests, physical examination, vital signs (systolic and diastolic blood pressures, respiratory rate, heart rate and body temperature) and 12-lead ECGs
Timepoint [1] 308201 0
During Part 1, subjects will be confined to the study unit and assessed from Day 1 to Day 3 before being discharged. They will return for follow up on Day 8 and Day 31. At the end of each dosing cohort a safety review committee will meet to review all available safety information to determine if it is safe to continue to the next dose level.
During Part 2, subjects will be confined to the study unit and assessed from Day 1 to Day 14 before being discharged. They will return for a follow up on Day 21 and Day 44. At the end of each dosing cohort a safety review committee will meet to review all available safety information to determine if it is safe to continue to the next dose level.
During Part 3, subjects will be confined to the study unit and assessed from Day 1 to Day 5 before being discharged. They will return to the study unit every 3 days from Day 5 until Day 27 when they will be re-confined until Day 30. They will return for a follow up on Day 35 and Day 58.
Secondary outcome [1] 354224 0
The following pharmacokinetic parameters will be measured in serum: Cmax, Tmax, AUC 0-last, kel, AUC 0-inf, t1/2, Tlag, CL/F, Vz/F, apparent terminal rate constant, MRT.
Timepoint [1] 354224 0
Part 1:
PK samples will be collected:
-prior to dosing on Day 1
- Samples will be collected at 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 30, 36 and 48 hours (± 10 minutes) post-dose.
-Day 8

Part 2
PK samples will be collected at:
-prior to dosing on Day 1
-1, 2, 3, 4, 6, 8, 12, 24 (pre-dose), 48 (pre-dose), 72 (pre-dose), and 96 hours (pre-dose) (± 10 minutes).
-Thereafter, collection of blood samples for measurement of serum PK will occur on Day 8 (pre-dose) and Day 11 (pre-dose).
-prior to dosing on Day 14
- Day 14 at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours (± 10 minutes) post-dose.
-Day 21

Part 3
PK samples will be collected at::
-prior to dosing on Day 1
-Day 1 at 1, 2, 3, 4, 6, 8, 12, 24 (pre-dose), 36, 48 (pre-dose), 72 (pre-dose), and 96 hours (pre-dose) (± 10 minutes).
-prior to dosing at onsite visits scheduled on Day 6, 10, 14 and Day 21 (± 1 day).
-Day 28 - pre dosing
-Day 28 at 1, 2, 3, 4, 6, 8, 12, 24, 36 and 48 hours (± 10 minutes) post-dose.
-Day 35

Secondary outcome [2] 354717 0
In Part 1 (SAD cohorts), Part 2 (MAD cohorts), and Part 3 (MD T2DM patient cohort) glycemic effect will be assessed: plasma glucose will be measured using a glucometer

.
Timepoint [2] 354717 0
Part 1

Plasma glucose will be collected at the following time points:
-Screening
-pre dose on Day 1
-Day 1
-Glycemic endpoints (blood glucose levels) will be assessed by a drop of blood from a finger prick or a venous blood sample taken for another purpose, by glucometer or another monitoring device at 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24 and 48 hours (± 10 minutes) post-dose.
-Day 8


Part 2

Plasma glucose will be collected at the following time points:
-Screening
-pre dose on Day 1
-Day 2, 3, and 5 i.e. at 24 (pre-dose), 48 (pre-dose) and 96 hours (pre-dose) following the first administered dose on Day 1 (± 15 minutes).
-2 hours prior to each dose administered on Day 8, 11 and 14
-Glycemic endpoints (blood glucose levels) will be assessed by a drop of blood from a finger prick or a venous blood sample taken for another purpose, by glucometer or another monitoring device from Day 1 at 1, 2, 3,4, 6, 8, 12, 16, 24 (pre-dose and before lunch and dinner), 48 (pre-dose and before lunch and dinner), 72 (pre-dose and before lunch and dinner), and 96 hours (pre-dose and before lunch and dinner) (± 10 minutes).
-Day 14 - prior to dosing
-Glycemic endpoints (blood glucose levels) will be assessed by a drop of blood from a finger prick or a venous blood sample taken for another purpose, by glucometer or another monitoring device from Day 14 at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours post-dose (Day 15 in fasting participants,).
-Day 21


Part 3

Plasma glucose will be collected at the following time points:
-Screening
- Day 1 to Day 5 - pre dose and post dose
-Glycemic endpoints (blood glucose levels) will be assessed by a drop of blood from a finger prick or a venous blood sample taken for another purpose, by glucometer or another monitoring device from Day 1 at 1, 2, 3, 4, 6, 8, 12, 16, 24 (pre-dose), 48 (pre-dose), 72 (pre-dose), and 96 hours (pre-dose) (± 10 minutes).
-Day 6 - 27 - Participants will monitor and record blood glucose levels 3 times per day or when symptomatic over the outpatient period.
-Day 14 and 21
-Day 28 - pre dose
-Day 35


Secondary outcome [3] 354748 0
In Part 1 (SAD cohorts from S2 onwards), Part 2 (MAD cohorts), and Part 3 (MD T2DM patient cohort)
• Composite endpoint: AUC for glucose, insulin, and C-peptide during meal tolerance test (MTT). Blood samples will be taken for measurement of glucose, insulin and C-peptide
Timepoint [3] 354748 0
Part 1 (second cohort onwards)

The Meal Tolerance Test will be performed at the following time points:
-Day 1, 3 hours post dose
Samples will be taken for analysis 60 mins prior to MTT and after start of meal ingestion, at 20 and 40 minutes and at 1.5, 2, 2.5, 3, 3.5 and 4 hours

Part 2
The Meal Tolerance Test will be performed at the following time points:
-Day 14 (3 hours post dose)
Samples will be taken for analysis 60 mins prior to MTT and after start of meal ingestion, at 20 and 40 minutes and at 1.5, 2, 2.5, 3, 3.5 and 4 hours

Part 3
The Meal Tolerance Test will be performed at the following time points:
-Day -1 (2 hours after admission)
-Day 28 3 hours post-dose
Samples will be taken for analysis 60 mins prior to MTT and after start of meal ingestion, at 20 and 40 minutes and at 1.5, 2, 2.5, 3, 3.5 and 4 hours
Secondary outcome [4] 354751 0
In Part 2 (MAD cohorts) and Part 3 (MD T2DM patient cohort) only
• Waist circumference
Timepoint [4] 354751 0
Part 2

Waist circumference will measured using a tape measure:
-at screening
-prior to dosing
-Day 14
-Day 21

Part 3

Waist circumference will be measured using a tape measure:
-at screening
-Day 29
-Day 35
Secondary outcome [5] 354754 0
       Part 3 (MD T2DM patient cohort) only
• HbA1c,


Timepoint [5] 354754 0
Blood samples will be collected on the following days:
-Screening
-Day 21
Secondary outcome [6] 354755 0
Part 3 (MD T2DM patient cohort) only
• Body composition (DEXA scan)
Timepoint [6] 354755 0
DEXA scans will be performed at:
-Screening
-Day 29

Eligibility
Key inclusion criteria
All study parts:
• Males and females aged 18-65 years (inclusive)
• Body mass index (BMI) 27-45 kg/m2
• No more than 5% weight loss within the preceding 3 months
• Normal blood pressure or well managed hypertension
• Females must be non-pregnant and non-lactating, and either surgically sterile
• Males must be surgically sterile, abstinent, or if engaged in sexual relations with a WOCBP, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion,
Part 1 only:
• Certified as healthy by comprehensive clinical assessment
Part 1 and 2:
• Fasting plasma glucose less than or equal to 100 mg/dL (6.0 mmol/L)
Part 2 and 3 only:
• Waist circumference greater than or equal to 102 cm (males) or greater than or equal to 88 cm (females)
Part 3 only:
• Confirmed diagnosis of T2DM
• If not antidiabetic medication naïve, participants must be on a stable dose metformin or a DPP-4 inhibitor or a combination of these for at least 3 months prior to study enrollment
• Fasting plasma glucose less than or equal to 90 mg/dL (5 mmol/L)
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnant or lactating, or intending to become pregnant within 30 days after last dose of study drug
• Participation in a clinical trial within 30 days before randomization; use of any experimental therapy within 30 days or 5 half-lives prior to randomization, whichever is greater; or use of any biologic therapy within 12 weeks or 5 half-lives prior to randomization, whichever is greater. Participants who have received an experimental therapy that has no half-life, like a vaccine, should have completed that therapy at least 12 weeks prior to randomization
• Any non-experimental vaccine within 12 weeks of randomization, until 4 weeks after the last dose, except for seasonal influenza vaccination which is permitted
• Use of any weight loss agent within 12 weeks prior to screening
• Surgery or hospitalization during the 4 weeks prior to screening
• Within the last 2 years, unstable or clinically significant cardiovascular disease

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)
sealed codebreak envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
simple randomisation using computer system
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
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)
VIC
Recruitment hospital [1] 12490 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 24869 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 301257 0
Commercial sector/Industry
Name [1] 301257 0
Carmot Therapeutics
Address [1] 301257 0
Carmot Australia First Pty Ltd., Tower 1, Level 16, Collins Square, 727 Collins Street, Melbourne VIC 3008, Australia
Country [1] 301257 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Carmot Therapeutics
Address
Carmot Australia First Pty Ltd., Tower 1, Level 16, Collins Square, 727 Collins Street, Melbourne VIC 3008, Australia
Country
Australia
Secondary sponsor category [1] 300893 0
Commercial sector/Industry
Name [1] 300893 0
Clinical Network Services
Address [1] 300893 0
Level 4, 88 Jephson Street, Toowong, QLD 4066
Country [1] 300893 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301998 0
Alfred Health Ethics Committee
Ethics committee address [1] 301998 0
Alfred Hospital, Commercial Road, Melbourne VIC 3004
Ethics committee country [1] 301998 0
Australia
Date submitted for ethics approval [1] 301998 0
31/10/2018
Approval date [1] 301998 0
30/11/2018
Ethics approval number [1] 301998 0

Summary
Brief summary
This study is designed to assess the safety and tolerability, pharmacokinetics (how the drug is absorbed by the body) and pharmacodynamics (the effect the drug has on the body) of CT-868 when administered as single and multiple ascending doses in overweight/obese (otherwise healthy) participants and as multiple doses in patient with type 2 diabetes mellitus. The study will start with a low single dose and safety information will be reviewed by a safety review committee to confirm if higher doses can be given to sequential cohorts before giving multiple doses.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88806 0
Dr Jason Lickliter
Address 88806 0
Nucleus Network, Level 5, Burnet Building, AMREP, Precinct, 89 Commercial Road, Melbourne VIC 3004
Country 88806 0
Australia
Phone 88806 0
+61 3 9076 8900
Fax 88806 0
Email 88806 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 88807 0
Mr Michael Elliott
Address 88807 0
Carmot Therapeutics, Inc.
740 Heinz Avenue
Berkeley, California 94710
Country 88807 0
United States of America
Phone 88807 0
+1 510 8256377
Fax 88807 0
Email 88807 0
melliott@carmot.us
Contact person for scientific queries
Name 88808 0
Mr Michael Elliott
Address 88808 0
Carmot Therapeutics, Inc.
740 Heinz Avenue
Berkeley, California 94710
Country 88808 0
United States of America
Phone 88808 0
+1 510 8256377
Fax 88808 0
Email 88808 0
melliott@carmot.us

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Commercial information
What supporting documents are/will be available?
No other documents available
Summary results
No Results