Part 1:Primary objective:• To estimate the relative bioavailability of two THB001 formulations in healthy adults.Secondary objectives:• To determine the single-dose pharmacokinetics (PK) of THB001•HCl salt and THB001 free base formulations in…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
allergic mediated diseases
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PK parameters including but not limited to: Cmax, tmax, t1/2, AUC0-t, and
AUC0-inf, dose normalized Cmax.
Secondary outcome
Safety and tolerability parameters including: physical examination, AEs,
clinical laboratory values, vital signs and 12-lead ECGs.
Background summary
Mast cells play a central role in the pathology of allergic-mediated diseases,
providing a strong rationale that depletion of mast cells can benefit patients
diagnosed with allergic mucosal and cutaneous disorders in which mast cell
degranulation plays a role in onset and progression. As a novel therapeutic
approach, mast cell depletion should inhibit multiple mediators of symptoms of
allergic diseases that have inadequate responses to single agents that target
only individual mediators of mast cells or whose off-target toxicity profiles
limit their use.
Mast cell activation, proliferation, and survival depend on the receptor
tyrosine kinase. Studies have shown that KIT mutations and kinase inhibition of
mutant KIT have profound effects on mast cells. Therefore, KIT is a
pharmacologically and genetically validated target to drive mast cell depletion.
THB001 is highly selective for KIT and, therefore, mast cell proliferation and
survival. The exquisite selectivity of THB001 was demonstrated in animals by
limited-to-no off-target toxicity and a defined on-target toxicity with a
reasonable therapeutic window. THB001 is expected to have robust mast cell
depletion and a favorable safety profile that supports clinical investigation.
Study objective
Part 1:
Primary objective:
• To estimate the relative bioavailability of two THB001 formulations in
healthy adults.
Secondary objectives:
• To determine the single-dose pharmacokinetics (PK) of THB001•HCl salt and
THB001 free base formulations in healthy adults.
• To assess the safety and tolerability of each treatment.
Part 2:
Primary objective:
• To assess the effect of dose and a high-fat meal on the bioavailability of
THB001•HCl salt.
Secondary objective:
• To characterize the plasma PK profile of a single oral dose of THB001•HCl
salt formulation in fasted and fed state in healthy adults.
• To assess the safety and tolerability of each treatment.
Study design
This is a single site, single dose, randomized, cross-over, 2-week, 2-arm,
2-part relative bioavailability (BA) study in healthy subjects.
Intervention
THB001 micronized blend free base as capsules.
Micronized THB001 HCl salt as capsules.
Study burden and risks
Since the study is being executed in healthy volunteers, there are no
anticipated benefits of the IMP. Please see the IB for further information.
300 Technology Square, 8th Floor 300 300
Cambridge MA 02139
US
300 Technology Square, 8th Floor 300 300
Cambridge MA 02139
US
Listed location countries
Age
Inclusion criteria
1. Subjects must understand the nature of the study and must provide signed and
dated written informed consent in accordance with local regulations before the
conduct of any study-related procedures.
2. Healthy as determined by the Investigator, based on a medical evaluation
including medical history, physical examination, laboratory tests and ECG
recording. A subject with a clinical abnormality or laboratory parameters
outside the reference range for the population being studied may be included
only if, in the opinion of the Investigator, the finding is (a) unlikely to
introduce additional risk to the subject, (b) will not interfere with study
procedures or confound study results, and (c) is not otherwise exclusionary
(see Exclusion Criteria).
3. Men and women, age 18-65 years inclusive at Screening will be enrolled.
4. Women of child-bearing potential must agree not to attempt to become
pregnant and to use a highly effective form of hormonal (excluding oral
contraceptives) or non-hormonal birth control, which entails the use of a
non-hormonal intra-uterine device/system in combination with a barrier method
(e.g. condom, diaphragm, cervical cap with spermicide) or abstinence during the
study and for 90 days after the last study drug administration. Postmenopausal
women must have had >=12 months of spontaneous amenorrhea (with documented
follicle-stimulating hormone (FSH) >=30 mIU/mL). Surgically sterile women are
defined as those who have had a hysterectomy, bilateral ovariectomy, or
bilateral tubal ligation. Women who are surgically sterile must provide
documentation of the procedure by a letter from their GP. All women must have a
negative pregnancy test result at Screening and on Day -1 before first
administration of study medication.
5. It is important that male subjects not impregnate others while in the study.
Therefore, male subjects who are biologically capable of having children must:
- Remain sexually abstinent, when this is in line with his preferred and usual
lifestyle.
OR
- Engage exclusively in same-sex relationships.
OR
- Agree to avoid impregnating his partner during the study (including washout
periods) and for at least 90 days after the last dose of study medication.
AND
- Must use a combination of two methods of contraception during the study
(including washout periods) and for at least 90 days after the last dose of
study medication. One of the contraceptive methods must be a condom with
spermicide (this is considered a single method). The second contraceptive
method must include one of the following: diaphragm in combination with a
spermicide; intrauterine device (IUD); contraception implant; progesterone-only
pills (POPs); injectable progestogen (Depo-Provera®); combination hormonal
contraceptive method (tablets, patches, or vaginal ring with both oestrogen and
progestogen), OR have a partner who had her last natural menstruation >=24
months prior to the Screening Visit, OR have a partner who was surgically
sterilized prior to the Screening Visit.
AND
- Not donate sperm during the study (including washout periods) and for at
least 90 days after the last dose of study drug.
OR
- Male subjects who have had a vasectomy at least 4 months prior to the
Screening Visit and must have completed post-surgical follow up to confirm
success of the vasectomy. Furthermore, they must agree to use a condom from Day
1 of the first treatment period until 90 days after the last dose of study drug
6. Subjects must be, in the opinion of the Investigator, able to participate in
all scheduled evaluations, likely to complete all required tests, and likely to
be compliant.
...
8. Subjects participating in Part 2 must be willing and able to consume the
entire high-fat, high-calorie breakfast meal in the designated timeframe.
Exclusion criteria
1. A positive urine drug screen/alcohol breath test at Screening or Day -1 of
the first treatment period.
2. A positive Hepatitis B surface antigen or positive Hepatitis C antibody
result at Screening.
3. A positive test for human immunodeficiency virus (HIV) antibody at
Screening.
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 | EUCTR2021-006627-18-NL |
| CCMO | NL80045.056.21 |