Clinical Trials Register

Summary
EudraCT Number:	2012-000181-37
Sponsor's Protocol Code Number:	CVT-301-002
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-27
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

UK - MHRA

A.2

EudraCT number

2012-000181-37

A.3

Full title of the trial

A Randomized, Placebo-Controlled Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of CVT-301 (Levodopa Inhalation Powder) in Patients with Parkinson’s Disease and Motor Response Fluctuations (“Off” Episodes)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study investigating the safety of CVT-301 in patients with Parkinson's Disease

A.4.1

Sponsor's protocol code number

CVT-301-002

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Civitas Therapeutics, Inc.
B.1.3.4	Country	United States
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	Civitas Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	i3 International (UK) Limited
B.5.2	Functional name of contact point	Global Regulatory Start-up Manager
B.5.3	Address:
B.5.3.1	Street Address	1st Floor Star House, 20 Grenfell Road
B.5.3.2	Town/ city	Maidenhead
B.5.3.3	Post code	SL6 1EH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00441628641884
B.5.5	Fax number	00441628408401
B.5.6	E-mail	i3regulatory@i3global.com

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	CVT-301
D.3.2	Product code	CVT-301
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVODOPA
D.3.9.1	CAS number	59-92-7
D.3.9.2	Current sponsor code	CVT-301
D.3.9.4	EV Substance Code	SUB08468MIG
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	12.5
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
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	No
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	Comparator
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	Yes
D.2.1.1.1	Trade name	Sinemet®
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	SINEMET® Plus 25 mg/100 mg Tablets
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVODOPA
D.3.9.1	CAS number	59-92-7
D.3.9.4	EV Substance Code	SUB08468MIG
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	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	38821-49-7
D.3.9.3	Other descriptive name	CARBIDOPA MONOHYDRATE
D.3.9.4	EV Substance Code	SUB21619
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	25
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)	No
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	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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	No
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	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Parkinson's Disease

E.1.1.1

Medical condition in easily understood language

Parkinson's Disease

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10034007
E.1.2	Term	Parkinson's disease NOS
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 characterize the safety and tolerability of inhaled CVT 301 in Parkinson’s disease patients experiencing “off” episodes

E.2.2

Secondary objectives of the trial

To characterize the input phase pharmacokinetic (PK) profile of single, inhaled doses of levodopa in patients with Parkinson’s disease experiencing “off” episodes

To evaluate the pharmacodynamics of single, inhaled doses of levodopa or a standard oral dose of levodopa in patients with Parkinson’s disease experiencing “off” episodes

Exploratory Objective
To describe and model the relationship of levodopa plasma concentration to motor response

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Has signed and dated an IEC-approved informed consent form before any protocol specific screening procedures are performed.
2. Has a clinical diagnosis of idiopathic PD (i.e., not induced by drugs or other diseases) as defined by fulfilling Steps 1 and 2 of the UK Brain Bank criteria, diagnosed at an age of 30 to 80 years, inclusive.
3. Is a male or female over the age of 30 years. Women of child-bearing potential must use protocol-defined contraceptive measures and must have a negative serum human chorionic gonadotropin (hCG) test at screening. These patients must be willing to remain on their current form of contraception for the duration of the study.
4. Is classified as Stage 1 to 3 (in the “on” state) on the modified Hoehn and Yahr scale for staging of PD severity.
5. Is levodopa-responsive (as documented by the investigator) with a PD medication regimen that includes a levodopa/DDI-containing regimen at least 4 times during the waking day. Levodopa-containing regimens must be stable for at least 2 weeks prior to
screening.
6. If treated with dopamine agonists, COMT inhibitors, MAO-B inhibitors, or other nonlevodopa-containing PD medications, must be on a stable dose for at least 4 weeks prior to screening and must remain stable throughout the study.
7. Has not received apomorphine for at least 2 weeks prior to screening and agrees not to be treated with apomorphine for the duration of the study.
8. Experiences motor fluctuations with recognizable and predictable “off” periods and has an average of at least 2 hours of “off” time per waking day, exclusive of early morning “off” time (by self-report). Patients should be able to recognize their “wearing off” symptoms and verify that they usually improve after their next dose of PD medication.
9. If a current smoker, is able to comply with the following guidelines: agrees not to smoke on the mornings of study dosing days and for the entire study dosing day until completion of all study procedures.
10. Is willing and able to complete all study assessments and procedures.
11. Has an FEV1 greater than 70% of predicted for race, age, sex, and height, and FEV1/FVC (forced vital capacity) ratio greater than or equal to 75%, in the “on” state.
12. Patients may be taking anti-depressant medication, but the dose must be stable for at least 4 weeks prior to screening.
13. Understands (with or without carer assistance) his/her daily PD medications.
14. Is able (with or without carer assistance) to attend all study visits.

E.4

Principal exclusion criteria

1. Is a pregnant or lactating woman.
2. Has severe dyskinesia that would significantly interfere with the patient’s ability to perform study assessments.
3. Has any condition that in the investigator’s opinion would make the patient unsuitable for participation in the study and/or medical condition that, in the opinion of the investigator, would interfere with participation in this study.
4. Has a history of chronic obstructive pulmonary disease (COPD), asthma, or other chronic respiratory diseases within the last 5 years, or is currently receiving treatment for any of these conditions.
5. Has used neuroleptics, reserpine, or catecholaminergic blocking agents within the last 3 months.
6. Has received dopamine agonist blocking agents and/or non-specific monoamine oxidase inhibitors (MAOIs) within the last 3 months; however, domperidone is allowed if the maximum daily dose does not exceed 60 mg and if the dose has been stable for at least 4 weeks prior to screening.
7. Has a history of psychotic symptoms requiring treatment with an antipsychotic medication within the past 12 months; however, certain low-dose atypical antipsychotic agents (prescribed for conditions other than psychosis) are allowed if the dose has been
stable for at least 8 weeks prior to screening (quetiapine ≤50 mg/day, risperidone ≤1 mg/day, and olanzipine ≤2.5 mg/day).
8. Has a history of suicidal ideation or suicide attempt within the past 12 months.
9. Has had previous surgery for PD or is planning stereotactic surgery during the study period.
10. In the opinion of the investigator (or carer, as applicable), has signs/symptoms suggestive of clinically significant cognitive impairment that would interfere with the ability to comply with study procedures.
11. Has a history of any primary malignancy, with the exception of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ or other malignancies curatively treated and with no evidence of disease for at least 3 years.
12. Has a history within 12 months prior to screening of substance-related disorders (with the exception of caffeine-related and nicotine-related disorders) as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR).
13. Has a QTcF interval of ≥450 msec for males or ≥470 msec for females, or has a clinically significant abnormal ECG as assessed by a qualified physician at screening.
14. Has any clinically significant abnormality following review of screening laboratory data, previous medical history or intercurrent illness, and physical examination data that, in the investigator’s opinion, may compromise the safety of the patient in the study.
15. Has been treated with an investigational drug within 4 weeks or 5 half-lives (whichever is longer) prior to the beginning of the screening period (this includes investigational formulations of marketed products).
16. Has had >500 mL of blood collected within 8 weeks prior to screening.

E.5 End points

E.5.1

Primary end point(s)

Pharmacokinetics
Baseline-adjusted maximum concentration (ΔCmax = Cmax - C0), time to maximum concentration (tmax), and baseline-adjusted partial area under the concentration-time curve (pAUC), e.g. at 5 0 (pAUC0-5) and 10 (pAUC0-10) minutes postdosing.

Pharmacodynamics
• Areas under the curve (AUC) from 0 - 3 hours.
• Average response for all assessments at 0 to 3 hours after the dose of study medication

• Best response for all assessments at 0-3 hours after the dose of study medication
• Early effect, defined as average response of assessments at 0-30 minutes after the dose of study medication

E.5.1.1

Timepoint(s) of evaluation of this end point

Pharmacokinetic Endpoints:
5 and 10 minutes post-dosing

Pharmacodynamic Endpoints:
Up to 3 hours post-dosing

E.5.2

Secondary end point(s)

Not Applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not Applicable

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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

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

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

Israel

Serbia

E.8.7

Trial has a data monitoring committee

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 Subject Last Visit

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

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects will continue with standard of care treatment after ending participation in the trial.

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

2012-04-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-11

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-11-29

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