Evaluate the effect of tedalinab on ECG parameters, CNS Function and Pain Perception in Healthy Subjects.
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Adverse events, pharmacokinetics results, ECG parameters
Secondary outcome
Cognitive function, pain perception and plasma beta-endorphin levels
Background summary
In animal toxicology studies, tedalinab was shown to slow heart rate and to
increase corrected QT interval (QTc) in all species (rat, monkey and dog)
studied. Animals in these trials were exposed at levels at least 5 fold higher
than those reached in studies in humans. In early human trials, ECG evaluations
failed to show a clear effect on QTc interval, however receipt of tedalinab
appeared to be associated with reductions in heart rate, most notable within 2
hours of dosing and noted more frequently during the multiple dose study. This
study is being performed to evaluate the effect, if any, of tedalinab on
cardiac intervals including QTc, using beat to beat analysis, which is thought
to be more appropriate for evaluating potential effects of compounds which have
an effect on heart rate.
Study objective
Evaluate the effect of tedalinab on ECG parameters, CNS Function and Pain
Perception in Healthy Subjects.
Study design
Phase I, Single-Centre, Randomized, Double-Blind, Placebo Controlled, Multiple
Dose
Intervention
Three different tedalinab dose regimens or matching placebo
Capsaicin/electrical evoked pain test
Cognitive test battery
Study burden and risks
The risks associated with this investigation are linked together with the
possible side effects of the investigational product (most important reported
adverse events were: skin rash, headache, dizziness and somnolence).
The burden on the volunteer will be the holter ECG monitoring,
neuropsychological tests, electrical pain treshold and tolerance test,
capsaicin evoked pain test, the venapunctions and the introduction of the
cannulas. All volunteers are closely monitored and supervised by experienced
doctors and study staff for possible side effects.
C2 7600 The Quorum
Oxford Business Park North, Oxford, OX4 2JZ
GB
C2 7600 The Quorum
Oxford Business Park North, Oxford, OX4 2JZ
GB
Listed location countries
Age
Inclusion criteria
• Male, 18-65 years (inclusive);
• Body weight >=60kg;
• Physical examination and laboratory safety evaluations within normal range for age;
• Willing to participate and provide written informed consent.
Exclusion criteria
• Allergy to tedalinab or any excipients;
• Subjects who have participated in an investigational drug study within 90 days prior to the dosing day;
• Hepatitis B, C or HIV infection;
• Subjects who have lost or donated >350 ml of blood within 12 weeks prior to the (first) dosing day;
• Subjects with clinically significant laboratory abnormalities;
• Subjects with an abnormal ECG at Screening or pre-dose, defined as:
o PR > 210 ms, or QRS complex > 120 ms, or QTc > 450 ms;
o Any cardiac conduction abnormalities;
o Any known structural abnormalities;
o Any clinically significant ST/T wave abnormalities;
o Any atrial or ventricular arrhythmias which are of clinical significance and may have an impact on the safety of the subject or the conduct of the study as judged by the PI;
• Subjects with a history of additional risk factors for torsade de pointes, e.g. a personal or family history of Long QT Syndrome;
• Subjects with a supine systolic blood pressure >160 mmHg or a supine diastolic blood pressure >90 mmHg;
• Subjects with a Body Mass Index (BMI) <18.0 or >29.0 kg/m2;
• Subjects who smoke (subjects will have to be non-smokers for at least 6 months preceding Screening);
• Subjects who have used prescription medication within 2 weeks prior to the first dosing day;
• Subjects who have used non-prescription medication, including aspirin, paracetamol, homeopathic medicines, vitamins, and herbal and dietary supplements within 96 hours pre-dose;
• Subjects with a presence or a history of clinically relevant conditions in the gastrointestinal, hepatic, renal, urogenital, metabolic, endocrine or central and peripheral nervous systems;
• Subjects with active presence or history of alcoholism or drug addiction;
• Subjects who are considered unsuitable to participate in the study for any reason in the opinion of the PI.
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 | EUCTR2010-021010-32-NL |
| CCMO | NL32692.056.10 |