Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000630910p
Ethics application status
Submitted, not yet approved
Date submitted
1/05/2020
Date registered
29/05/2020
Date last updated
29/05/2020
Date data sharing statement initially provided
29/05/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of increasing oral doses of INCB106385 in healthy adult participants, and the effect of food on pharmacokinetics, as well as drug interaction with a Proton Pump Inhibitor (PPI) esomeprazole.
Scientific title
A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Single Dose, Dose-Escalation, Drug-Interaction, and Food-Effect Study to Assess the Safety, Tolerability, and Pharmacokinetics of INCB106385 When Administered Orally to Healthy Adult Participants
Secondary ID [1] 301001 0
INCB 106385-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors 317041 0
Condition category
Condition code
Cancer 315204 315204 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
INCB106385 is an oral tablet administered after a fast of 8 hrs. in cohorts 1 through 5 (dose escalation cohorts). In Cohort 6 (food effect cohort) participants will be randomly assigned to treatment A or treatment B groups and then crossed over to the other treatment group (A or B) after a washout of 7 days. Participants in treatment A group will be dosed after fasting of 8 hrs. Participants in treatment B group will be fed a high-fat calorie meal before 30 min of dose administration. Participants will be admitted to the clinic on the day -1 before study drug administration and confined through 96 hours after the dosing. In Cohort 6 participants will return on Day 7 for admission and receive another dose of the drug on Day 8 and be confined through 96 hours after dosing. In Cohort 7, drug interaction with esomeprazole (a proton pump inhibitor, PPI) will be evaluated. All participants will receive the same dose of INCB106385 in the fasted state alone or with esomeprazole.
Cohort 1 - up to 5 mg of INCB106385 or Placebo as a single dose administered orally in a fasted condition
Cohort 2 - up to15 mg of INCB106385 or Placebo as a single dose administered orally in a fasted condition
Cohort 3 - up to 40 mg of INCB106385 or Placebo as a single dose administered orally in a fasted condition
Cohort 4 - up to 100 mg of INCB106385 or Placebo as a single dose administered orally in a fasted condition
Cohort 5 -up to 200 mg of INCB106385 or Placebo as a single dose administered orally in a fasted condition
Cohort 6 - up to 100 mg of INCB106385 in Fasted or Fed conditions as a single dose administered orally
Cohort 7 - up to 100 mg of INCB106385 administered orally in Fasted condition on Day 1 and 40 mg of esomeprazole is administered orally on days 5 through 9 under fed conditions and a combination of INCB106385 (100 mg) and esomeprazole (40 mg) administered in fasted conditions on day 10.
Intervention code [1] 317337 0
Treatment: Drugs
Comparator / control treatment
Placebo tablets have been developed to match the INCB106385 1 mg and 10 mg tablets are similar in appearance to the active drug product tablets with regard to color, size, and shape, and contain microcrystalline cellulose, mannitol, crospovidone, silicon dioxide, and magnesium stearate. The placebo tablets will also be coated with a nonfunctional white film coat.
Control group
Placebo

Outcomes
Primary outcome [1] 323487 0
Number of treatment-emergent adverse events with INCB106385.
As this is the first clinical study of INCB106385 the safety profile in humans has not been established. Possible symptoms or adverse effects that could occur may be immune-related effects such as inflammation of the skin or mucosa (for example, itching, redness, rash), inflammation of the lungs, inflammation of the bowels (for example, diarrhea), endocrine (hormone) dysfunction, liver injury, and fatigue or lack of energy. AE's will be assessed by clinical examination.
Timepoint [1] 323487 0
Baseline to 31 days after last dose
Primary outcome [2] 323488 0
Pharmacokineitc (PK) evaluation of INCB106385(Cmax, Tmax, AUC0-t and AUC 0-inf)in the fasted and fed state
Timepoint [2] 323488 0
0h(pre dose), 0.5,1,2,4,6,8,12,16h post dose.
Primary outcome [3] 323489 0
Pharmacokinetic (PK) evaluation of INCB106385 and to assess the effect of the Proton Pump Inhibitor (PPI), esomeprazole on the PK(Cmax, Tmax, AUC0-t and AUC 0-inf) of INCB106385
Timepoint [3] 323489 0
0h(pre dose), 0.5,1,2,4,6,8,12,16h post dose
Secondary outcome [1] 382050 0
Additional Pharmacokinetic parameter evaluation in Plasma include t½, CL/F, Vz/F, lambda-z
Timepoint [1] 382050 0
0h(pre dose), 0.5,1,2,4,6,8,12,16h post dose
Secondary outcome [2] 382051 0
Pharmacokinetic evaluation of INCB106385 in Urine include
Ae96h and CLR
Timepoint [2] 382051 0
0 to 8, 8 to 16, 16 to 24, 24 to 36, 36 to 48, 48 to 72, and 72 to 96 hours post dose

Eligibility
Key inclusion criteria
1. Male or female healthy adult participants aged 18 to 55 years
2. BMI between 18.0 and 30.0 kg/m2, inclusive. Participants with a BMI up to 32.0 kg/m2 may be enrolled with the sponsor’s approval.
3. Willingness to avoid pregnancy or fathering children.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of uncontrolled or unstable cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening.
2.History or presence of an abnormal ECG before initial dose administration that, in the investigator's opinion, is clinically significant. QTcF interval > 450 milliseconds, QRS interval > 120 milliseconds, and PR interval > 220 milliseconds
3.Current or recent (within 3 months of screening) clinically significant gastrointestinal disease or surgery (including cholecystectomy) that could affect the absorption of study drug except that appendectomy will be allowed.
4.Donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of screening (within 2 weeks for plasma only).
5.History of alcoholism within 3 months of screening.
6.Positive urine, blood, or breath test for ethanol or positive urine or serum screen for drugs of abuse that are not otherwise explained by permitted concomitant medications or diet.
7.Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug with another investigational medication or current enrollment in another investigational drug protocol.
8.History of any significant drug allergy (such as anaphylaxis or hepatotoxicity) deemed clinically relevant by the investigator.
9.Use of tobacco- or nicotine-containing products within 1 months of screening.
10.Women who are pregnant or breastfeeding.
11.Any history of hypersensitivity or intolerance to esomeprazole or any other Proton Pump Inhibitor
Reason

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
27/07/2020
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 305445 0
Commercial sector/Industry
Name [1] 305445 0
Incyte Corporation
Country [1] 305445 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Incyte Corporation
Address
1815 Augustine Cut Off, Wilmington, DE 19803
Country
United States of America
Secondary sponsor category [1] 305870 0
None
Name [1] 305870 0
Address [1] 305870 0
Country [1] 305870 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 305762 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 305762 0
The Alfred
55 Commercial Road, Melbourne VIC 3004
Ethics committee country [1] 305762 0
Australia
Date submitted for ethics approval [1] 305762 0
06/05/2020
Approval date [1] 305762 0
Ethics approval number [1] 305762 0

Summary
Brief summary
The purpose of this study is to assess the safety, tolerability of the drug INCB106385 and assess how this drug acts in the body with and without food in increasing doses and assess how this drug interacts with esomeprazole, a PPI.
You may be eligible for this study if you are a male or female, aged 18 to 55, and you are in good health with no existing conditions. All participants will provide blood and urine samples.
Participants in this study will be randomized (by chance) in each of the 7 cohort. In Cohorts 1-5, all participants will either receive a single dose of the drug or placebo (orally in a fasted condition (no food).
In Cohort 6 all participants will be randomly assigned to treatment A or treatment B groups and then crossed over to the other treatment group (A or B) after a washout of 7 days. Participants in treatment A group will be dosed after fasting of 8 hrs. Participants in treatment B group will be fed a high-fat calorie meal before 30 min of dose administration.
In Cohort 7 all participants will be dosed with drug on day 1 and dosed with esomeprazole on day 5-9 and on day 10 participants will be dosed with drug and esomeprazole.
It is hoped this research will provide information as to how this drug acts in the body in fed and fasted conditions and the impact of changes in gut pH. Results from the study will affect how patients with cancer take the drug in regards to their meals.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 101506 0
Prof Ben Snyder
Address 101506 0
Centre for Clinical Studies
Level 5, Burnet Tower, 89 Commercial Rd
Melbourne, Victoria 3004
Country 101506 0
Australia
Phone 101506 0
+61 0390768960
Fax 101506 0
Email 101506 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 101507 0
Ben Snyder
Address 101507 0
Centre for Clinical Studies
Level 5, Burnet Tower, 89 Commercial Rd
Melbourne, Victoria 3004
Country 101507 0
Australia
Phone 101507 0
+61 0390768960
Fax 101507 0
Email 101507 0
b.snyder@nucleusnetwork.com.au
Contact person for scientific queries
Name 101508 0
Ben Snyder
Address 101508 0
Centre for Clinical Studies
Level 5, Burnet Tower, 89 Commercial Rd
Melbourne, Victoria 3004
Country 101508 0
Australia
Phone 101508 0
+61 0390768960
Fax 101508 0
Email 101508 0
b.snyder@nucleusnetwork.com.au

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


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.