This study is being performed to evaluate the cognitive and psychomotor effects of the new compound LY2624803 after bedtime dosing.
ID
Source
Brief title
Condition
- Sleep disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the cognitive and psychomotoric effects of LY2624803,
diphenhydramine and zolpidem after bedtime dosing in healthy volunteers.
Secondary outcome
-Determine the cognitive and psychomotor effects of LY2624803 at 5 and 8 hours
post-evening dose (after a first awakening at 2 hours post dose) on periods 1-4
-Determine the cognitive and psychomotor effects of LY2624803 at 5 and 8 hours
post-evening dose (after a first awakening at 5 hours post dose) on period 5
-Explore the relationship between the cognitive and psychomotor tests and
LY2624803, zolpidem and diphenhydramine doses and exposures.
Background summary
LY2624803 is a new research drug developed by Eli Lilly for the potential
treatment of insomnia. It is believed to act in a more specific way than
existing drugs. Therefore it is expected to have less unfavourable side-effects
compared to existing drugs. Diphenhydramine and zolpidem are two examples of
such existing drugs used commonly to treat insomnia. Since these drugs are
taken at bedtime, their side-effects may cause problems when waking up
unexpectedly during the night.
The purpose of this study is to investigate the cognitive and psychomotor
effects of LY2624803 and zolpidem in part A and of diphenhydramine, zolpidem
and LY2624803 in part B. Part A and part B consist of 5 separated study periods
each.
Study objective
This study is being performed to evaluate the cognitive and psychomotor effects
of the new compound LY2624803 after bedtime dosing.
Study design
This study is a phase I, single dose, randomized, double-blind, 5 periods
cross-over, placebo-controlled, 2-cohort study to evaluate the Cognitive and
Psychomotor effects of LY2624803 following bedtime dosing in healthy subjects.
Study burden and risks
Study drug side-effects:
LY2624803
As of March 2008, LY2624803 has been taken by 115 people (107 men and 8 women).
The most common bad effects seen in more than 1 person who have taken LY2624803
include feeling worn out, headache, feeling dizzy, having an upset stomach
(nausea), nosebleeds, runny nose, and nightmares. Additionally, an increase in
the number of heartbeats each minute was observed in 9 out of 10 people who had
been given a 10-mg dose. An increase in the number of heartbeats per minute
may be noticeable as a fluttering or pounding in the chest, or may be
accompanied by feelings of tiredness or dizziness. Taking LY2624803 could
affect your ability to perform activities that require mental alertness, such
as operating machinery or driving a car.
Zolpidem
Zolpidem is a registered sedative used for the treatment of insomnia. It may
commonly cause drowsiness the following day, headache, dizziness, numbed
emotions, reduced alertness, confusion, vertigo, gastro-intestinal
disturbances, double vision, skin reactions and amnesia. Zolpidem could affect
your ability to perform activities such as operating machinery or driving a car
Diphenhydramine
Diphenhydramine is a registered drug used for the treatment of nightly
awakening and initial insomnia. It may commonly cause dizziness, drowsiness and
grogginess. Diphenhydramine could affect your ability to perform activities
such as operating machinery or driving a car.
Rare side effects:
LY2624803
LY2624803 has been studied in animals. Information on bad effects in animals
may predict possible risks to humans. Animals treated with high doses of
LY2624803 showed uncoordinated movement, problems with walking, uncontrollable
shaking (convulsions), or death. High doses of LY2624803 have also produced
increased blood pressure in animals. The doses that you receive will be much
lower than the doses given to animals at which the above bad effects were
noted. Studies in animals also suggest that humans may be at risk for seizures.
However, no seizures have been reported by subjects taking LY2624803 and are
not expected in humans at the doses administered clinical trials. Taking
LY2624803 may also cause dizziness when standing up. One may even faint when
feeling dizzy if not sitting or lying down until the dizziness is gone. One man
given a 6-mg dose of LY2624803 became dizzy and was observed to have a low
blood pressure when standing. He did not faint or require special treatment.
Another man given a 3 mg-dose of LY2624803 fainted shortly after standing up
from bed. For a brief period of time medical personnel were unable to determine
if his heart was beating. This is not unusual in such an event and was not life
threatening. He regained consciousness without special treatment and recovered
completely. If you have a history of fainting or dizziness upon standing you
may be at greater risk for these problems if you receive LY2624803.
Zolpidem
Zolpidem is a registered drug. The risk of unforeseen side-effects is therefore
not greater than with other drugs. Fatigue, muscle weakness, ataxia, decreased
libido and paradoxical reactions occur seldomly.
Diphenhydramine
Diphenhydramine is a registered drug. The risk of unforeseen side-effects is
therefore not greater than with other drugs. Dryness of the mouth, nausea and
nervousness occur seldomly.
Burden (see also section E4 of this form):
-no chocolate, cola, coffee or tea during 8 hours prior to the study day and
during the study day. It is also not allowed to administer more than 5 units
within 48 hours prior to the study day;
-smoking is not allowed during each study day and it is not allowed to smoke
more than 5 sigarettes a day within 21 days prior to the study;
-use of adequate contraceptives during the study and 3 months after the sudy;
-use of alcohol is not allowed during 24 hours prior to the study day and
during the study day. Male subjects are not allowed to consume more than 28
units a week and female subjects are not allowed to consume more than 21 units
a week;
-go to bed not more than one hour earlier or one hour later than usual for the
2 nights prior to each study period.
-subjects have to wear the actigraph during 24 hours prior to the study day.
Indianapolis
46285 Indiana
Verenigde Staten
Indianapolis
46285 Indiana
Verenigde Staten
Listed location countries
Age
Inclusion criteria
1. Provision of written informed consent
2. Healthy male and female subjects aged 18 to 45 years or 65-85 years on sceening
3. Body Mass Index (BMI) >= 19 and <= 30 kg/m2
Exclusion criteria
1.Investigator site personnel or Lilly employees directly affiliated with this study
and their immediate families. Immediate family is defined as a spouse, parent,
child or sibling, whether biological or legally adopted.
2.Shift workers (those who shifted work within 7 days of any study night) or any
person who has crossed (or will have crossed) more than one time zone by aircraft
within 3 days prior to each study night.
3.Rhinoconjunctivitis, urticaria, chronic pain or nocturia that, in the investigator*s
opinion, would interfere with sleep assessment.
4.Previously diagnosed sleep disorder including chronic insomnia, sleep apnea,
narcolepsy or restless leg syndrome, or current symptoms consistent with a sleep
disorder.
5.Insomnia caused by a psychiatric, neurological or medical disease within the past
12 months.
6.Irregular or altered sleep/wake schedule interpreted by the investigator.
7.History of loss of consciousness due to explained or unexplained syncope or
orthostatic signs and symptoms such as dizziness, tachycardia or hypotension.
History of loss of consciousness due to cranial trauma will be discussed prior to
including any such subject (See Section 6.4.1.3 for orthostatic measurement
procedure).
8.Known history of epilepsy (except a single febrile convulsion) or a family history
of seizures.
9.Use of prescription, over the counter or herbal medications (other than oral
contraceptive treatment or hormonal replacement therapy) that can safely be
discontinued within 21 days prior to enrollment. Subjects over 65 yrs of age, on a
stable dose (>= 3 months prior to screening) of one medication for lowering
cholesterol, triglycerides and/or one medication for lowering blood pressure
and/or substitutive hormonal therapy in post menopausal women are allowed
provided those treatments have no clinically significant central nervous system
adverse effects. See Section 5.6 Concomitant Therapy, for sample list of
acceptable medication.
10.Enrolment in another concurrent investigational study or intake of an
investigational drug within 3 months prior to the start of the study or more than 4
times a year.
11. Known allergies or contraindications to LY2624803, zolpidem, diphenhydramine
or related compounds.
12.Persons who have previously completed or withdrawn from this study or any
other study investigating LY2624803 or HY10275
13.An abnormality in the 12-lead ECG that, in the opinion of the investigator,
increases the risks associated with participating in the study.
14.History or presence of clinically significant cardiovascular, respiratory, hepatic,
renal, gastrointestinal, endocrine, haematological, neurocardiogenic or
neurological disorders capable of significantly altering the absorption,
metabolism, or elimination of drugs; of constituting a risk when taking the study
medication; or of interfering with the interpretation of data.
15.Any other condition which in the opinion of the investigator would preclude
participation the study.
16.Current regular use (including "recreational uses") of any illicit drugs (including
cannabis) confirmed by positive urine drug screen at screening or any study day,
or a history of drug or alcohol abuse.
17.Positive Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C test.
18.Women who are lactating.
19.Blood donation of more than 500 mL within the last 3 months.
20.Subjects who have an average weekly alcohol intake that exceeds 28 units per
week (males) and 21 units per week (females), or subjects unwilling to stop
alcohol consumption for at least 24 hours prior to admission to the CRU until
being discharged from the CRU (1 unit = 12 oz or 360 mL of beer; 5 oz or
150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
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 | EUCTR2008-001929-34-NL |
| CCMO | NL23384.058.08 |