Clinical Trials Register

Summary
EudraCT Number:	2009-015565-31
Sponsor's Protocol Code Number:	4305-009
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-10-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Sweden - MPA

A.2

EudraCT number

2009-015565-31

A.3

Full title of the trial

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Long Term Safety Study of MK-4305 in Patients with Primary Insomnia

A.4.1

Sponsor's protocol code number

4305-009

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme (Sweden) AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MK-4305
D.3.2	Product code	MK-4305
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MK-4305
D.3.2	Product code	MK-4305
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Primary Insomnia

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.0
E.1.2	Level	LLT
E.1.2	Classification code	10036701
E.1.2	Term	Primary insomnia

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of of MK-4305 for up to 12 months of treatment.

E.2.2

Secondary objectives of the trial

1. To evaluate the efficacy of MK-4305 compared with placebo in improving insomnia, as measured by change from baseline in subjective total sleep time (sTST) on the sleep diary during the first month of treatment (using the average of weekly measurements [Weeks 1, 2, 3 and 4]).

2. To evaluate the efficacy of MK-4305 compared with placebo in improving insomnia, as measured by change from baseline in subjective time to sleep onset (sTSO) on the sleep diary during the first month of treatment.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient is male or female and ≥18 years of age on the day of signing informed consent.
2. Patient has a DSM-IV-TR (Appendix 6.2) diagnosis of Primary Insomnia based on the investigator’s judgment and the patient’s sleep history as assessed on the Sleep Diagnostic Interview/Sleep History.
3. For a patient ≥65 years of age, (s)he scores ≥25 on the Mini Mental State Examination (MMSE), to rule out cognitive impairment in the interest of safety for the patient. NOTE: If <65 years old, answer "YES" except in cases where administration of the MMSE to the patient <65 seems indicated in the opinion of the investigator.
4. A female patient who is of reproductive potential has a serum β-hCG level consistent with the nongravid state at Screening Visit 1 and agrees to use acceptable contraception. Acceptable contraception is defined as abstinence (where abstinence is a locally accepted form of contraception) or use of 2 regionally accepted effective non-hormonal forms of contraception including: partner using condom with spermicide or status post vasectomy, and patient using intra-uterine device (IUD), diaphragm with spermicide, contraceptive sponge. Note that if a male partner does not use an effective form of contraception, a female patient MUST use 2 acceptable forms of contraception to satisfy the study requirement.
5. Patient demonstrates compliance with the morning and evening diary for the period between Visit 2 and 3. Diary compliance is defined as patient having completed at least 70% [e.g. 5 out of 7 days/nights] of both the morning and evening diaries.

E.4

Principal exclusion criteria

1. Patient has a recent and/or active history of a confounding neurological disorder, including but not limited to: seizure disorder (other than single episodes of childhood febrile seizures), stroke, transient ischemic attack, multiple sclerosis, cognitive impairment, or significant head trauma with sustained loss of consciousness and residual impairment within the last 10 years.
2. Patient has either a history within the past 6 months prior to the Screening Visit 1 or current evidence of an unstable or otherwise clinically significant cardiovascular disorder, including but not limited to:
acute coronary syndrome
unstable angina,
congestive heart failure
cardiogenic syncope
cardiomyopathy
any symptomatic arrhythmia
3. Patient has abnormal screening laboratory values per the guidelines below, or in the opinion of the investigator has any other clinically significant laboratory abnormality:
Alanine transaminase (SGPT or ALT) > 1.5 times the upper limit of normal (x ULN)
Aspartate transaminase (SGOT or AST) > 1.5 x ULN
Total bilirubin > 1.5 x ULN
Serum creatinine of > 2 mg/dL
4. Patient is taking, or plans to take, one or more of the following medications (non-inclusive), shown below, within the specified washout periods prior to Screening Visit 2 and throughout the course of the study:
Investigational compounds-4 weeks or 5 t½ lives (which ever is longer)
Clinically relevant CYP3A4 Inhibitors and Inducers-2 weeks or 5 t½ lives (which ever is longer)
Centrally acting anticholinergics or antihistamines-2 weeks
Melatonin-2 weeks
Anticonvulsants-2 weeks
Antipsychotics-2 weeks
Anxiolytics-2 weeks
Benzodiazepines-2 weeks or 5 t½ lives (which ever is longer)
Hypnotics-2 weeks or 5 t½ lives (which ever is longer)
Any CNS depressants-2 weeks
Over-the-counter medications that could affect sleep [e.g., kava-kava, valerian, Benadryl (diphenhydramine) St. Johns wort] -2 weeks
Stimulants-2 weeks
Diet pills-2 weeks

5. Patient has any of the following:
a. A lifetime history of bipolar disorder, a psychotic disorder, or posttraumatic stress disorder;
b. A psychiatric condition requiring treatment with a prohibited medication; or
c. Other current psychiatric condition that, in the investigator's opinion, would interfere with the patient's ability to participate in the study.
6. Patient has evidence of suicidality (based on a score of ≥ 2 on the QIDS-SR16 suicide item #12) or, in the investigator's opinion, is otherwise impaired in such a way as to be unable to complete the study procedures in a safe and appropriate fashion (regardless of QIDS-SR16 score).
7. Patient, in the opinion of the Investigator, has difficulty sleeping due to tobacco, caffeine, or alcohol use.
8. Patient has a history of malignancy ≤ 5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
9. Patient has a history of transmeridian travel (across > 3 time zones or > 3 hour time difference) within the past 2 weeks.
10. Patient has a history of shift work (defined as permanent night shift or rotating day/night shift work) within the past 2 weeks or anticipates need to perform shift work during the study.
11. Patient has a history or diagnosis of any of following conditions, in the opinion of the investigator:
a. Narcolepsy
b. Cataplexy (familial or idiopathic)
c. Circadian Rhythm Sleep Disorder
d. Parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, and REM behavior disorder
e. Sleep-related Breathing Disorder (obstructive or central sleep apnea syndrome, central alveolar hypoventilation syndrome)
f. Periodic Limb Movement Disorder
g. Restless Legs Syndrome
h. Primary Hypersomia
12. In the opinion of the investigator, patient has difficulty sleeping due to a confounding medical condition. NOTE: “Medical Conditions” may include chronic pain syndromes, chronic migraines, cardiac disease, nocturia (>3 times/night), asthma, gastroesophageal reflux disease (GERD), or hot flashes.
13. The patient has a Body Mass Index (BMI) > 40 kg/m2. BMI is calculated by taking the subject’s weight in kg and dividing by the subject’s height in meters, squared.

E.5 End points

E.5.1

Primary end point(s)

• adverse experiences (AEs),
• laboratory values,
• ECGs,
• physical examinations,
• vital signs,
• rebound insomnia and withdrawal effects.
• The Columbia - Classification Algorithm of Suicide Assessment (C-CASA) scores from the C-SSRS will also be evaluated

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last Patient Last Vist.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2009-10-09.	Yes
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	50
F.4.2	For a multinational trial
F.4.2.1	In the EEA	470
F.4.2.2	In the whole clinical trial	750

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2009-12-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-11-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-08-01

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