The purpose of the study is to investigate how safe the compound USL260 is and how well the compound USL260 is tolerated under fasting and fed conditions. The study will also investigate how quickly and to what extent the compound USL260 is absorbed…
ID
Source
Brief title
Condition
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety, tolerability and pharmacokinetic profile.Food effect.
Secondary outcome
Not applicable.
Background summary
The drug to be given Tonabersat (USL260) is a new, investigational compound
that may eventually be used for the treatment of migraine. Migraine is a
disorder characterised by attacks of throbbing headache
lasting from 4 to 72 hours (most commonly around 24 hours) accompanied by
nausea, vomiting and sensitivity to light and sounds. Tonabersat is a new
compound which has a broader range of activity than the commonly used
anti-migraine agent, sumatriptan.
Current treatment of migraine with sumatriptan gives cardiovascular- and
neurotoxic effects. It is expected that treatment with Tonabersat (USL260) is
expected to give less cardiovascular (faster -or slower hartbeat,
heartpalpitations) and neurotoxic effects (cold fingers and/or cold feet).
Study objective
The purpose of the study is to investigate how safe the compound USL260 is and
how well the compound USL260 is tolerated under fasting and fed conditions. The
study will also investigate how quickly and to what extent the compound USL260
is absorbed and eliminated from the body (this is called pharmacokinetics)
under fasting and fed conditions.
This study is not intended to improve your health, but is necessary for the
further development of the compound.
Study design
A Phase 1 Randomized, Placebo-controlled, Double-Blind, Multiple Dose, Parallel
Arm Study to Evaluate the Effect of Meal timing and Food versus the Fasted
State on the Safety, Tolerability and Pharmacokinetics of Repetitive Daily
Doses of USL260.
In Group 1 and 2 you will receive the study drug or placebo 30 minutes after
the start of a standard high fat breakfast. Group 3will receive the study drug
or placebo after a period of minimal 10 hours fasting. If you take part on
Group 4 you will receive a breakfast at 1 hour post dose, which you have to eat
completely. Group 5 will receive the study drug or placebo 2 hours after the
start of a breakfast, that the volunteers have to eat completely. All doses
will be administrated as one or more tablets together with 240 ml of water at
room temperature.
In each group 10 volunteers will receive the drug USL260 and 2 volunteers will
receive placebo.
The screening will include a physical examination including measurement of
blood pressure and pulse rate, a heart trace (electrocardiogram) recording, and
a number of blood and urine tests. You will also be screened for drugs of abuse
and alcohol. Hepatitis A, B and C, and HIV (= AIDS test). In case of female
participants a pregnancy test will be performed. The volunteer will be asked to
complete a questionnaire (CSSR) about potential depressive feelings.
The post-study examination will include a complete physical examination
including measurement of blood pressure and pulse rate, a heart trace
(electrocardiogram) recording, and a number of blood and urine tests, alcohol,
drug of abuse and a pregnancy test. You will also be asked to complete a
questionnaire (CSSR) about potential depressive feelings.
Both for the pre-study screening and the post-study follow-up examination, the
volunteer will have to be fasted (not to have eaten or drunk anything, except
water). For the pre-study screening the volunteer will have to be fasted for at
least 4 hours and for the post-study follow-up you will have to be fasted for
at least 10 hours.
Intervention
Group Day Study drug Dose Frequency Condition
(4*80mg)
1 1-14 USL260/Placebo 320 mg Once daily Fed state
2 1-14 USL260/Placebo 80 mg Once daily Fed state
3 1-14 USL260/Placebo 320 mg Once daily Fasted state
4 1-14 USL260/Placebo 320 mg Once daily 1 hour before a breakfast
5 1-14 USL260/Placebo. 320 mg Once daily 2 hours after a breakfast.
All doses will be administrated as one or more tablets together with 240 ml of
water at room temperature.
In each group 10 volunteers will receive the drug USL260 and 2 volunteers will
receive placebo.
Study burden and risks
Previous clinical studies were conducted with the same compound in 221 healthy
volunteers (148 males and 73 females), and 44 patients with migraine (9 males
and 35 females). In addition, multiple dose studies have been conducted in 39
patients with a diagnosis of migraine with aura (10 males and 29 females).
Migraine with aura is a migraine that's preceded or accompanied by a variety of
sensory warning signs or symptoms, such as flashes of light, blind spots or
tingling in your hand or face. In these studies doses up to 200 mg daily for a
maximum of 14 days have been administered to volunteers and the following
adverse effects were reported or observed: nausea, dizziness, sleepiness,
headache and vertigo. Scotoma described as an area of lost vision or a *blind
spot* in the field of vision was also reported. In addition the following
serious adverse events have been reported: low blood pressure and epileptic
seizure ; lowering of blood potassium with vomiting, dehydration and dizziness;
sigmoid diverticulitis, complex migraine and left sided weakness, all
considered to be possibly related to the study medications and the subjects
were withdrawn.
Currently there is an ongoing study with single ascending doses up to 400 mg in
60 subjects and multiple ascending doses up to 400 mg in 48 subjects. The most
common adverse events in the single- and multiple ascending dose parts of this
study that were possibly or probably related were; dizziness, impaired
coordination, reduced concentration, headache intermittent orthostatic
intolerance, light headiness, bad taste, nausea and vomiting, hot flushes,
sleepiness, restlessness, and gastrointestinal disorders. Most adverse events
were of mild or moderate intensity. In the multiple ascending part one subject
experienced a rash of severe intensity. This adverse event is possibly related
to the study medication.
The insertion of the indwelling canula and the venepuncture may cause some
pain, and sometimes lead to a bruise, but the actual collection of blood will
not be painful. Light bleeding and possibly an infection may occur. Infusion
may cause oedema in the arm where the infusion is given. However, chances these
complications will occur are limited.
6701 Evenstad Drive North
MN 55369-6026 Maple Grove, Minnesota,
US
6701 Evenstad Drive North
MN 55369-6026 Maple Grove, Minnesota,
US
Listed location countries
Age
Inclusion criteria
* Age 18 to 65 years, inclusive. ;* Male or non-pregnant and not breast feeding female (non-pregnancy will be confirmed by a serum pregnancy test conducted at Screening and prior to any dosing period).;Female subjects of childbearing potential must be:;o On oral contraceptive therapy; or,;o Practicing acceptable double-barrier methods of birth control during the course of the study (e.g., a barrier method using a condom with spermicide, diaphragm with spermicide, or cervical cap with spermicide); or ;o Surgically sterile (bilateral tubal ligation 90 days or more prior to dosing, bilateral oopherectomy, or hysterectomy).;Female subjects who are post- menopausal must be:;o Postmenopausal (no menses) for at least 1 year and have a documented follicle stimulating hormone (FSH) level *30 mIU/ml.;o Post-menopausal females may be on hormone replacement therapy.;* Have a body mass index (BMI) between 18 and 30 kg/m2, inclusive, and weigh at least 50 Kg (110 lbs.).;* Physical examination is within normal limits; a subject with a clinical abnormality could be included only if the investigator considers that it would not introduce any additional risk to the subject nor interfere with study procedures.;* Grapefruit juice is not allowed 7 days prior to dosing, throughout the entire clinic period (through Day 21), and until after the completion of Day 28 PK blood samples are collected. ;* Theobromide-, alcohol-, caffeine-, and xanthine-containing beverages or food (coffee, tea, cola beverages, chocolate, *power drinks*) are not allowed for 48 hours (2 days) prior to dosing, throughout the entire clinic period, until the morning of Day 28.;* All hematology and clinical chemistry values for blood and urine are within the normal range or show no relevant deviations as judged by the medical investigator.;* Subject is a *light smoker*, i.e., he/she smokes no more than 5 cigarettes (1/4 pack) per day.;* Is able to communicate effectively with study personnel and are considered reliable, able, willing and cooperative with regard to complying with protocol-defined requirements as assessed by the study investigator.;* Can voluntarily give written informed consent to participate in the study prior to the completion of any study-related procedures.
Exclusion criteria
* Have a clinically relevant current illness (within 4 weeks prior to dosing) or history of a medical condition that would interfere with the subject*s ability to complete the study or would confound the results of this study, as determined by the clinical investigator(s).;* Have a predisposing condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs or any condition that may confound the analyses to be conducted in this study. ;* Have evidence of clinically relevant pathology.;* Have a clinically significant history of renal or hepatic disease or gastrointestinal disease.;* Have history of malignancy, suspicious or undiagnosed skin lesions, or a history of melanoma.;* Have history of psychoses, depression, suicidal ideation (as determined by CSSR assessment) or tendencies (within 1 year of the Screening Visit).;* Have past history of or current, severe cardiovascular or pulmonary disease, bronchial asthma, or endocrine disease including diabetes or hypoglycemia.;* Have history of lactose intolerance or lactose sensitivity. ;* Have a history of, or currently observed, clinically significant arrhythmias as evidenced on Screening ECG, or history of myocardial infarction that has residual atrial, nodal, or ventricular arrhythmias, or any other clinically significant cardiac disease ;* a systolic blood pressure of above 140 mm Hg or diastolic blood pressure of above 90 mm Hg or a systolic blood pressure of below 90 mm Hg or diastolic blood pressure of below 50 mm Hg.;* Have a history of, or currently observed, clinically significant CNS disorder.;* Have history of complications from venipunctures.;* Have donated blood or plasma within 60 days prior to the Screening Visit.;* Have a history of clinically significant alcohol or significant psychoactive substance use disorder (abuse, dependence, and/or withdrawal) within the past 12 months (within 1 year of the Screening Visit).;* Have a positive drug screen for drugs of abuse at Screening or upon admission.;* Have a positive test for human immunodeficiency virus (HIV), HAV IgM (to assess recent hepatitis A infection), hepatitis B, or hepatitis C.;* Have taken a prescription medication, including MOA inhibitors, within 14 days prior to the initial PK study period or taken over-the-counter oral preparations, including dietary and herbal supplements, 3 days prior to dosing.;* Previous exposure to USL260 or its metabolite. Have required continuation of previous concomitant medications other than those allowed (see Section X.X) during the study.;* Have participated in another clinical trial with any other investigational drug within 30 days prior to the first PK study period.
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 | EUCTR2011-004837-15-NL |
| CCMO | NL38357.056.11 |