To evaluate the safety, tolerability and pharmacokinetics (PK) of TV 1380 in healthy male and female subjects following multiple intramuscular (IM) injections.
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Cocaineverslaving en cocaine-overdosis
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
Pharmacokinetics: Serum TV-1380 concentrations, pharmacokinetics parameters
Safety: Adverse events, vital signs, ECG-parameters, local tolerability,
laboratory parameters, physical examination
Additional evaluations are: BChE and AChE activity, immunogenicity and ex vivo
hydrolysis
Secondary outcome
n/a
Background summary
The drug to be given, TV-1380, is a new, investigational compound that may
eventually be used for the treatment of cocaine addiction or cocaine overdose.
TV-1380 is still in the developmental phase. If there is cocaine in the body
systems, TV-1380 rapidly eliminates it from the brain, heart and periphery by
facilitating the degradation of cocaine. In the absence of cocaine, the drug is
not expected to have any pharmacological effect. You will be getting only the
drug, with no cocaine in your body. During the study, you will not be given any
cocaine or any other drugs of abuse and you are not allowed to take any either.
This new compound is not registered as a drug but has been given to humans
before in other clinical studies.
Study objective
To evaluate the safety, tolerability and pharmacokinetics (PK) of TV 1380 in
healthy male and female subjects following multiple intramuscular (IM)
injections.
Study design
Design:
This will be a double-blind, placebo-controlled, parallel-group, escalating
multiple dose study in three cohorts of healthy subjects receiving TV-1380.
Within each dose group subjects will be randomly assigned to receive either
TV-1380 (8 subjects) or placebo (3 subjects). Each subject will receive
once-weekly injections of TV-1380 for 4 weeks.
Procedures and assessments
Screening and follow-up:
Medical history, demographic data, vital signs, physical examination, alcohol
and drug screen, HBsAg, anti HCV, anti-HIV 1/2 and pregnancy test (females
only), clinical laboratory (including clinical chemistry, haematology,
coagulation and urinalysis), previous and concomitant medication, 12-lead
electrocardiogram (ECG) and BChE and AChE activity; at eligibility screening:
vital signs, drug and alcohol screen, pregnancy test (females only), 12-lead
ECG, clinical laboratory (including clinical chemistry, haematology,
coagulation and urinalysis), gross neurological exam, immunogenicity, BChE and
AChE activity and ex vivo cocaine hydrolysis.
Observation period:
4 in-house periods: 2 periods of 4 days (Day -1 until 3, and Day 21 until 24)
en 2 periods of 3 days (Day 7 until 9, and Day 14 until 16), and 7 ambulatory
visits (Day 5, 12, 19, 26, 29, 32 and 36)
Blood sampling:
for pharmacodynamics for serum TV-1380: pre-dose and 1, 2, 4, 6, 8, 12, 18, 24,
36, 48, 96, 168, 180, 192, 264, 336, 348, 360, 432, 504, 505, 506, 508, 510,
512, 516, 522, 528, 540, 552, 600, 672 and 744 h post first dose.
for immunogenicity: pre-dose Day 8, 15, 22 and 29.
for BChE and AChE activity: pre-dose Day 8, 15, 22 and 29.
for ex vivo cocaine hydrolysis: pre-dose Day 5, 8, 12, 15, 19, 22, 26 and 29.
Safety assessments:
Adverse events and concomitant medication: throughout the study; vital signs:
pre-dose and 1, 4, 8, 24, 48, 96, 168, 264, 336, 432, 504, 600, 672 and 744 h
post first dose; gross neurological exam: Day 2, 9, 16 and 23; clinical
laboratory: Day 3, 5, 7, 12, 14, 19, 21 and 29; 12-lead ECG: pre-dose and 1, 4,
8, 24, 48, 96, 168, 264, 336, 432, 504, 600, 672 and 744 post first dose;
extensive ECG: Pre-dose (-55 minutes, -35 minutes, and -15 minutes before first
dosing) and 503.08 (-55 minutes), 503.42 (-35 minutes), 503.75 (-15 minutes
before fourth dosing), 504, 506, 508, 512, 516, 528, 540, 552, 600 and 672 h
post first dose; local tolerability and pain: 1, 2, 4, 8 and 24 h post each
dose.
Bioanalysis:
analysis of serum TV-1380 samples using a validated method by Sponsor
analysis of ex-vivo cocaine hydrolysis using a clinical chemistry method by
Sponsor
analysis of BChE and AChE activity using a validated method by Sponsor
Intervention
Active substance : TV-1380
Activity : cocaine hydrolysis
Indication : cocaine addiction
Strength : 30 mg vial with 1.1 ml sterile water for injection
Dosage form : intramuscular injection
Treatments:
Group 1: a single intramuscular injection of 50 mg TV-1380 or placebo on Day 1,
8, 15 and 22
Group 2: a single intramuscular injection of 150 mg TV-1380 or placebo on Day
1, 8, 15 and 22
Group 3: a single intramuscular injection of 300 mg TV-1380 or placebo on Day
1, 8, 15 and 22
Study burden and risks
Procedures: pain, light bleeding, aematoma, possibly an infection.
9471 GP Zuidlaren
NL
9471 GP Zuidlaren
NL
Listed location countries
Age
Inclusion criteria
Healthy male and female volunteers, 18-45 years of age, BMI between 18.0 and 30.0 kg/m2; weight is at least 50 kg, no smokers for at least 3 months
Exclusion criteria
Suffering from: hepatitis B, 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 90 days from the start of the study. In case of donating more than 1.5 liters of blood in the 10 months prior the start of this study.
Design
Recruitment
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 | EUCTR2011-004856-20-NL |
CCMO | NL38620.056.11 |