Clinical Trials Register

Summary
EudraCT Number:	2018-002233-37
Sponsor's Protocol Code Number:	IPX203-B16-02
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-01-24
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2018-002233-37

A.3

Full title of the trial

A randomized controlled study to compare the safety and efficacy of IPX203 with immediate-release carbidopa-levodopa in Parkinson's disease patients with motor fluctuations.

A.3.1

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

Evaluate the safety and efficacy of IPX203 carbidopa-levodopa extended release capsules compared to carbidopa-levodopa immediate release tablets in patients with Parkinson’s with motor fluctuations.

A.4.1

Sponsor's protocol code number

IPX203-B16-02

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03670953

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	Impax Laboratories, LLC
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	Impax Laboratories, LLC
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	Impax Laboratories, LLC
B.5.2	Functional name of contact point	Drug Safety Dept. Attn: Dr. Sanwo
B.5.3	Address:
B.5.3.1	Street Address	50 Horse Block Road
B.5.3.2	Town/ city	Brookhaven, NY
B.5.3.3	Post code	11719
B.5.3.4	Country	United States
B.5.4	Telephone number	+1877 835-5472, option 1
B.5.5	Fax number	+1631 924 5145
B.5.6	E-mail	DrugSafety@Amneal.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	IPX203
D.3.2	Product code	IPX203
D.3.4	Pharmaceutical form	Modified-release capsule, hard
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.3.9.2	Current sponsor code	LD
D.3.9.3	Other descriptive name	LEVODOPA
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	140
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carbidopa
D.3.9.2	Current sponsor code	CD
D.3.9.3	Other descriptive name	ANHYDROUS CARBIDOPA
D.3.9.4	EV Substance Code	SUB22639
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	35
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.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	Carbidopa and Levodopa Tablets, USP
D.2.1.1.2	Name of the Marketing Authorisation holder	Mylan Pharmaceuticals Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	IR CD-LD (carbidopa-levodopa) tablets
D.3.2	Product code	IR CD-LD
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.3.9.2	Current sponsor code	LD
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.3.8	INN - Proposed INN	Carbidopa
D.3.9.2	Current sponsor code	CD
D.3.9.3	Other descriptive name	ANHYDROUS CARBIDOPA
D.3.9.4	EV Substance Code	SUB22639
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	Capsule, hard
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

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10061536
E.1.2	Term	Parkinson's disease
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029205
E.1.2	Term	Nervous system disorders
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10028035
E.1.2	Term	Movement disorder
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 evaluate the safety and efficacy of IPX203 in comparison to IR CD-LD in the treatment of CD-LD-experienced subjects with Parkinson’s disease who have motor fluctuations.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female subjects diagnosed at age ≥ 40 years with PD, consistent with the United Kingdom Parkinson’s Disease Society Brain Bank Diagnostic Criteria and who are being treated with stable regimens of CD-LD but experiencing motor fluctuations.
• Hoehn and Yahr Stages 1, 2, 3, or 4 in the “On” state (part of Movement Disorders Society version of the Unified Parkinson’s Disease Rating Scale [MDS-UPDRS] Part III)
• Montreal Cognitive Assessment (MoCA) score ≥ 24 at Screening Visit in “On” state.
• By history, for the 4 weeks prior to Screening, the subject experiences daily “wearing-off” episodes with periods of bradykinesia in combination with at least one of rest tremor or rigidity, experiences an “Off” state upon awakening on most mornings, and reports an average of at least 2.5 cumulative hours per day of “Off” time during the waking hours.
• Able to differentiate “On” state from “Off” state as determined by at least 75% concordance with a trained rater in “On/Off” ratings for 8 ratings over a 4-hour training period. The concordance must include at least 1 “On” and 1 “Off” rating and must be achieved within two 4-hour training sessions.
• At Visit 1, review of the 3-day PD Diaries confirms the following: that the subject is able to properly complete the Diaries with valid entries; and that the subject has an average of at least 2.5 hours per day of “Off” time during waking hours over the 3 days with at least 1.5 hours of cumulative “Off” time on each day.
• Responsive to CD-LD therapy and currently being treated on a stable regimen with CD-LD for at least 4 weeks prior to Visit 1 and:
− Requires at least 100 mg of LD from IR CD-LD for the first morning dose;
− Requires a total daily dose of at least 400 mg of LD and takes a maximum total daily dose of 2400 mg LD, from IR CD-LD alone or IR CD-LD in combination with a single daily bedtime dose of CR CD-LD;
− Has a dosing frequency of 4 to 9 times daily of CD-LD;
− By history, typically experiences an “On” response with the first dose of IR CD-LD of the day, but the efficacy of this dose typically lasts less than 4 hours.
• At Screening, the subject has predictable “Off” periods defined by a score of 1 or 2 on Item #4.5 (Complexity of Motor Fluctuations) of the MDS-UPDRS Part IV B (Motor Fluctuations).
• At Screening, the MDS-UPDRS Part III total score in the “Off” state is at least 20 units.

E.4

Principal exclusion criteria

• Used any doses of controlled-release (CR) CD-LD apart from a single daily bedtime dose within 4 weeks prior to Visit 1.
• Used any dose of Rytary for the past 4 weeks prior to Visit 1 or were considered IPX066 or Rytary failures for reasons of efficacy or safety.
• Had prior neurosurgical treatment for PD or if such procedure is planned or anticipated during the study period.
• Allergic to any excipient in the study drugs.
• History of glaucoma with intraocular pressures that are elevated despite appropriate medical management.
• History of seizure or epilepsy and experienced at least 1 seizure during the past 12 months or has not been compliant with medically recommended therapy or visits.
• History of myocardial infarction with residual atrial, nodal, or ventricular arrhythmias that are not controlled with medical and/or surgical interventions. A recent (≤ 12 months) history of myocardial infarction with secondary arrhythmias is exclusionary regardless of the therapeutic control.
• Received within 4 weeks of Screening or planning to take during participation in the clinical study:
− Any doses of a CR CD-LD apart from a single daily bedtime dose, any doses of Rytary, additional CD (eg, Lodosyn) or benserazide (eg, Serazide), or catechol-O-methyl transferase inhibitors (entacapone or tolcapone) or medications containing these inhibitors (Stalevo);
− Nonselective monoamine oxidase inhibitors (MAOI), apomorphine, or antidopaminergic agents, including antiemetics.
• Subjects who have previously participated in an IPX203 study.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in “Good on” time in hours per day, averaged over the PD Diary days, at the end of double-blind treatment period (Visit 7 or early termination). “Good on” time is derived from the 3-day PD Diaries and is defined as the sum of “On” time without dyskinesia and “On” time with nontroublesome dyskinesia.

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 7 or early termination

E.5.2

Secondary end point(s)

− Change from baseline in “Off” time in hours per day, averaged over the PD Diary days at the end of double-blind treatment period;

− Proportion of subjects with either “much improved” or “very much improved” in Patient Global Impression of Change (PGI-C) scores at the end of double-blind treatment period;

− Change from baseline in the MDS-UPDRS Part III at the end of double-blind treatment period;

− Change from baseline in the sum of MDS-UPDRS Parts II and III at the end of double-blind treatment period.

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 7 or early termination

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

Yes

E.8.1.7.1

Other trial design description

double-dummy

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

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

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

Canada

Czech Republic

France

Germany

Italy

Poland

Spain

United Kingdom

United States

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

LVLS

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:

265

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

245

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

266

F.4.2.2

In the whole clinical trial

510

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)

Open label extension study planned for subjects who completed this main IPX203-B16-02 study.

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

2020-04-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-02-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-06-15

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