The study will be performed in 3 parts, Parts 1, 2 , 3. and 4 (DDI). The purpose of the study is to investigate how safe the compound is and how well the compound is tolerated; this will be investigated in all study parts. In Parts 1 and 2, it will…
Source
Brief title
Condition
- Leukaemias
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Safety and Tolerability
Secondary outcome
Pharmacokinetics
Pharmacodynamics
Background summary
The drug to be given is a new investigational compound that may eventually be
used for the treatment of inflammatory diseases. The study medication is still
under development. It is thought to inhibit the action of specific proteins
found in white blood cells. As white blood cells play a role in the immune
system, the study medication may influence specific parts of the immune system.
As such, it may be used in the treatment of inflammatory disorders and also of
blood malignancies. The study medication is being developed as an orally
administered compound and will be given as capsules in this study.
Study objective
The study will be performed in 3 parts, Parts 1, 2 , 3. and 4 (DDI). The
purpose of the study is to investigate how safe the compound is and how well
the compound is tolerated; this will be investigated in all study parts. In
Parts 1 and 2, it will also be investigated how quickly and to what extent the
compound is absorbed and eliminated from the body (this is called
pharmacokinetics). In Part 3, the effect of food on pharmacokinetics of the
compound will be investigated. In addition, in Parts 1 and 2 the effect of the
compound on specific proteins present in the body will be investigated (this is
called pharmacodynamics).
In Part 4, is to assess the effect of ketoconazole on the plasma PK of the
compound will be investigated (IPI-145).
Study design
A randomized, double blind, placebo controled study with single (Part 1) or
multiple (Part 2) dosing of the study medication and a randomized, open label
study study the effect of food on the absorption of the study medication (Part
3)
Part 4 will be a non-randomized, open-label, single-sequence study design with
1 cohort of 16 healthy male and/or healthy female subjects to assess the effect
of ketoconazole on the plasma PK of IPI-145 (drug-drug interaction [DDI]).
Pre study screening:
Informed consent, medical history, demographics, clinical laboratory (clinical
chemistry, hematology, coagulation and urinalysis), physical examination, 12
lead electrocardiogram (ECG) in triplicate, vital signs (blood pressure, pulse,
respiratory rate and body temperature), height, weight, Body Mass Index (BMI)
calculation, drug and alcohol screen, serology (hepatitis B surface antigen
(HBsAg), anti hepatitis C virus (HCV) antibodies and anti human
immunodeficiency virus (HIV) 1/2 antibodies), serum pregnancy test and follicle
stimulating hormone (females only), Quantiferon Gold test, previous and
concomitant medication, and eligibility check
Between Days -28 and Day -3 (Part 2 only) :
Antigen placement for delayed type hypersensitivity (DTH) skin tests (test will
be read approximately 48 hours later), previous and concomitant medication, and
adverse events (AEs)
Admission (all parts) :
Clinical laboratory (clinical chemistry, hematology, coagulation and
urinalysis), physical examination, 12-lead ECG in triplicate, vital signs
(blood pressure, pulse, respiratory rate and body temperature), weight, serum
pregnancy test (females only), drug and alcohol screen, previous and
concomitant medication, AEs and eligibility check
Follow-up (all parts) :
Clinical laboratory (clinical chemistry, hematology, coagulation and
urinalysis), physical examination, 12-lead ECG in triplicate, vital signs
(blood pressure, pulse, respiratory rate and body temperature), serum pregnancy
test (females only), blood sampling for immunoglobulin (Ig) E, IgG, IgM and IgA
assessment (Part 2 only), blood sampling for immunophenotyping (Part 2 only),
blood sampling for potential cytokine analysis (Part 2 only), previous and
concomitant medication, and AEs
Part 1 (SAD)
Observation period :
One period in clinic from -18 h up to 72 h after drug administration.
Blood sampling :
For PK of IPI-145 and metabolites in plasma: at pre-dose and at 0.5, 1, 1.5, 2,
3, 4, 6, 9, 12, 16, 24, 36, 48 and 72 h post-dose
For potential assessment of the PD markers basophil activation, or p-S6 and
p-AKT in whole blood or peripheral blood mononuclear cells (PBMCs),
respectively: at pre-dose and at 1, 2, 4, 6, 12 and 24 h post dose
For genotyping (this is optional for each subject) (cytochrome P450 (CYP)
isozymes, uridine diphosphate glucuronyltransferase (UDPGT) enzymes and/or drug
transporters): at pre-dose
For metabolite profiling in plasma: at pre-dose and at 2 and 12 h post-dose
Urine collection :
For PK of IPI-145 and metabolites and for metabolite profiling: at pre-dose
(within 24 hours prior to dosing) and over 0 3, 3-6, 6-12, 12 24, 24-48 and
48-72 h post-dose collection intervals
Safety assessments :
AEs: recorded from admission until completion of the follow up visit and a
specific inquiry regarding AEs will be conducted at the following time points:
at 2, 4, 12, 24, 36, 48 and 72 h post-dose, and at the follow-up visit;
clinical laboratory (clinical chemistry, hematology, coagulation and
urinalysis): at 24, 48 and 72 h post-dose; 12-lead ECG (in triplicate): at
pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48 and 72 h post
dose; vital signs (blood pressure, pulse, respiratory rate and body
temperature): at pre-dose and at 1, 2, 3, 4, 6, 12, 24, 48 and 72 h post-dose;
physical examination: at discharge
Part 2 (MAD)
Observation period :
One period in clinic from -18 h before drug administration on Day 1 up to 72 h,
but no less than 24 h after final drug administration on Day 14. The
observation period may be shortened depending on the PK results obtained in
Part 1
Blood sampling :
For PK of IPI-145 and metabolites in plasma: at pre-dose and at 0.5, 1, 1.5, 2,
3, 4, 6, 9, 12, 16, 24 h post-dose on Days 1 and 14. Additional samples will be
taken prior to the morning dose on Days 11, 12 and 13 and at 36, 48 and 72 h
post-dose on Day 14
For potential assessment of the PD markers basophil activation, or p-S6 and
p-AKT in whole blood or PBMCs, respectively: at pre-dose and at 1, 2, 4, 6, 12
and 24 h post-dose on Days 1 and 14
For IgE, IgG, IgM and IgA assessment (safety): at pre-dose on Days 1, 7 and 14
For genotyping (this is optional for each subject) (CYP isozymes, UDPGT enzymes
and/or drug transporters): at pre dose on Day 1
For metabolite profiling in plasma: at pre-dose on Days 1 and 14 and at 2 and
12 h post dose on Day 14
For potential cytokine analysis (PD): at pre-dose on Days 1 and 14 and around
tmax (from Part 1) on Day 14
For immunophenotyping (PD): at pre-dose on Days 1, 7 and 14
Urine collection :
For PK of IPI-145 and metabolites and for metabolite profiling: at pre-dose
(within 24 hours prior to dosing) and over a 0 12 h post-dose collection
interval on Days 1 and 14
DTH skin tests :
Antigens placed on Day 11 and skin test read approximately 48 hours later on
Day 13
Safety assessments :
AEs: recorded from the day of antigen placement for the DTH test until
completion of the follow up visit and a specific inquiry regarding AEs will be
conducted prior to each dose, at 24 hours post-dose on Day 14, prior to release
from the clinic on Day 17, and at the follow-up visit; clinical laboratory
(clinical chemistry, hematology, coagulation and urinalysis): pre-morning dose
on Days 3, 7, 10, and 14, and at discharge on Day 17; 12 lead ECG (in
triplicate): at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12 and 24 h post-dose
on Day 1, and at pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, 24, 36, 48 and 72
h post-dose on Day 14; vital signs (blood pressure, pulse, respiratory rate and
body temperature): at pre-dose and at 1, 2, 3, 4, 6, 12 and 24 h post-dose on
Days 1 and 14, and at 2 h after the morning dose on Days 2-13; physical
examination: at discharge
Part 3 (FE)
Observation period :
Two periods in clinic from -18 h up to 72 h, but no less than 24 h after drug
administration, with a wash out period of at least 7 days between dose
administrations in individual subjects. The observation period may be shortened
depending on the PK results obtained in Part 1
Blood sampling :
For PK of IPI-145 and metabolites in plasma: at pre-dose and at 0.5, 1, 1.5, 2,
3, 4, 6, 9, 12, 16, 24, 36, 48 and 72 h post-dose. The blood sampling schedule
may be shortened depending on the PK results obtained in Part 1
For genotyping (this is optional for each subject) (CYP isozymes, UDPGT enzymes
and/or drug transporters): at pre dose (first dose administration only)
Safety assessments :
AEs: recorded from admission until completion of the follow up visit and a
specific inquiry regarding AEs will be conducted at the following time points:
at 2, 4, 12, 24, 36, 48 and 72 h post-dose, and at the follow-up visit;
clinical laboratory (clinical chemistry, hematology, coagulation and
urinalysis): at 24, 48 and 72 h post-dose; 12-lead ECG (in triplicate) and
vital signs (blood pressure, pulse, respiratory rate and body temperature): at
pre-dose and at 2 and 72 h post-dose; physical examination: at discharge
Analysis (all parts) :
Bioanalysis of plasma and urine samples for IPI-145 and metabolites using
validated methods by PRA
Metabolite profiling in plasma by the Sponsor
Genotyping of CYP isozymes, UDPGT enzymes and/or drug transporters by Sponsor
Potential assessment of the PD markers basophil activation, or p-S6 and p-AKT
in whole blood or PBMCs, respectively using flow cytometry analysis by PRA
Immunophenotyping using flow cytometry analysis by PRA
Potential cytokine analysis by the Sponsor
Clinical laboratory (clinical chemistry, hematology, coagulation, urinalysis,
and IgE, IgG, IgM and IgA) by PRA.
Part 4 DDI):
Observation period:
One period in clinic from -18 h before IPI-145 administration on Day 1 up to 48
h after final IPI-145 administration on Day 6.
Blood sampling:
For PK of IPI-145 and metabolites in plasma: at pre-dose and at 0.5, 1, 2, 3,
4, 6, 9, 12, 24, 36 and 48 h following IPI-145 administration on Days 1 and 6.
Genotyping (this is optional for each subject) (CYP isozymes, UDPGT enzymes
and/or drug transporters): at pre dose (first IPI-145 administration only).
Intervention
Active substance: IPI-145 or placebo
In Part 2: 2 times DTH (subcutaneus injection of anti-bodies) with tetanus,
candida, trichopython and tuberculin.
Study burden and risks
Procedures: pain, light bleeding, heamatoma, possibly an infection.
780 Memorial drive
MA 02139 Cambridge
US
780 Memorial drive
MA 02139 Cambridge
US
Listed location countries
Age
Inclusion criteria
Age: 18 * 55 years, inclusive
BMI: 18.0 * 30.0 kg/m2, inclusive
Exclusion criteria
Suffering from: hepatitis B, C, cancer or HIV/AIDS. In case of participation in another drug study within 60 days before the start of this study or being a blood donor within 60 days from the start of the study or in case of donating more than 1.5 liter (for men)/ 1.0 liter (for women) of blood in the 10 months prior the start of this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2011-001944-31-NL |
CCMO | NL37462.056.11 |