Clinical Trials Register

Summary
EudraCT Number:	2016-000723-94
Sponsor's Protocol Code Number:	LP101-CL-201
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-05-17
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2016-000723-94

A.3

Full title of the trial

A Phase 2, Multicenter, Randomized, Double-Blind, Comparator-Controlled Study of the Efficacy, Safety, and Pharmacokinetics of Intravenous Ulimorelin (LP101) in Patients with Enteral Feeding Intolerance

Estudio de fase II, multicéntrico, aleatorizado, doble ciego, controlado con comparador, para evaluar la eficacia, la seguridad y la farmacocinética de ulimorelina (LP101) administrada por vía intravenosa en pacientes con intolerancia a la alimentación enteral

A.3.1

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

A.4.1

Sponsor's protocol code number

LP101-CL-201

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	Lyric Pharmaceuticals, 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	Lyric Pharmaceuticals, 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	Pivotal, S.L.
B.5.2	Functional name of contact point	Paz González
B.5.3	Address:
B.5.3.1	Street Address	Gobelas 19
B.5.3.2	Town/ city	Madrid
B.5.3.3	Post code	28023
B.5.3.4	Country	Spain
B.5.4	Telephone number	003491708 12 55
B.5.5	Fax number	003491708 13 01
B.5.6	E-mail	pivotalregulatoryunit@pivotal.es

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	Ulimorelin
D.3.2	Product code	LP101
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ulimorelin
D.3.9.2	Current sponsor code	LP101
D.3.9.3	Other descriptive name	ULIMORELIN HYDROCHLORIDE MONOHYDRATE
D.3.9.4	EV Substance Code	SUB31967
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Metoclopramide
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	Metoclopramide
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METOCLOPRAMIDE
D.3.9.1	CAS number	364-62-5
D.3.9.2	Current sponsor code	metoclopramide
D.3.9.3	Other descriptive name	metoclopramide
D.3.9.4	EV Substance Code	SUB08902MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Enteral Feeding Intolerance

Intolerancia a la alimentación Enteral

E.1.1.1

Medical condition in easily understood language

Enteral Feeding Intolerance

Intolerancia a la alimentación Enteral

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10074293
E.1.2	Term	Enteral feeding intolerance
E.1.2	System Organ Class	100000004861

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 efficacy of multiple daily intravenous (IV) doses of ulimorelin on the proportion of the target daily protein received through enteral nutrition by mechanically ventilated and tube-fed patients with enteral feeding intolerance (EFI)

Evaluar el efecto de varias dosis diarias de ulimorelina, administradas por vía intravenosa (i.v.), sobre el porcentaje del objetivo proteico diario deseado que reciben a través de nutrición enteral pacientes con intolerancia a la alimentación enteral (IAE) sometidos a ventilación mecánica y alimentados por sonda.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of multiple daily IV doses of ulimorelin on the proportion of the target daily calories received through enteral nutrition by mechanically ventilated and tube-fed patients with EFI

Evaluar el efecto de la administración de varias dosis diarias de ulimorelina, administradas por vía intravenosa (i.v.), sobre el porcentaje del objetivo calórico diario deseado que reciben a través de nutrición enteral pacientes con intolerancia a la alimentación enteral sometidos a ventilación mecánica y alimentados por sonda.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Men and non-pregnant women aged 18 years and above
2.Intubated and mechanically ventilated in the ICU
3.Receiving continuous nasogastric, orogastric, or percutaneous gastric tube feeding, with no contraindication to advancing feedings per the feeding protocol (Appendix 9.5)
4.A 12-Fr or larger nasogastric, orogastric, or percutaneous gastric feeding tube, with its distal tip at least 10 cm below the gastroesophageal junction and visible in the stomach on a routine radiographic examination within 24 hours of screening
5.Enteral feeding intolerance, defined as a GRV of ≥ 500 mL on one or more measurements [N.B., a follow-on GRV < 500 mL prior to randomization will not exclude study participation]
6.Expected to remain intubated, mechanically ventilated, and receiving nasogastric feeding for at least 72 hours

1.Hombres y mujeres no embarazadas con una edad mínima de 18 años
2.Intubados y con ventilación mecánica en la UCI
3.Que estén recibiendo alimentación continua por sonda nasogástrica, orogástrica o gástrica percutánea, sin contraindicaciones para aumentar las tomas según el protocolo de alimentación
4.Que tengan colocada una sonda de alimentación nasogástrica, orogástrica o gástrica percutánea de 12 French o mayor cuyo extremo distal se encuentre al menos 10 cm por debajo de la unión gastroesofágica y se pueda ver en un examen radiológico ordinario realizado en las 24 anteriores a la selección.
5.Intolerancia a la alimentación enteral, definida como un VGR ≥ 500 ml en una o más determinaciones
6.Se prevé que permanecerá intubado, con ventilación mecánica y alimentación por sonda nasogástrica como mínimo durante 72 horas

E.4

Principal exclusion criteria

1.Inability to obtain written informed consent to participate in the study from the patient or legally authorized representative. (Whenever possible, patients who participate based on proxy consent will be re-consented once deemed capable by the Investigator of providing consent on their own.)
2.Prior use during the current ICU admission of parenteral nutrition or trophic feeding defined as a prescription to receive ≤ 20 mL/hr of enteral feeding for more than 24 hrs prior to screening [N.B., parenteral nutrition may be initiated post randomization provided that the supplemental nutrition is coordinated with the calories and protein targets of the PTV and reduced as enteral feeding is advanced]
3.Weight prior to ICU admission exceeding 150.0 kg
4.Positive serum pregnancy test at screening in women of child-bearing potential (a serum pregnancy test needs to be performed only once and does not need to be repeated prior to randomization)
N.B., Women of child-bearing potential must abstain from sexual intercourse or use effective birth control methods for 1 month after their participation in the study ends. Men with a female partner capable of having children must abstain from sexual intercourse or use effective birth control methods for 3 months after their participation in the study ends (see Section 3.5.2.11).
5.Suspicion or confirmation of active bowel obstruction, perforation, or leakage
6.History of esophageal or gastric surgery prior to or during the current hospital admission
7.History of diabetic, neurogenic, or idiopathic gastroparesis (patients will only be excluded if one of these disorders is documented in the medical record prior to admission to the ICU)
8.Conditions associated with excessive GH secretion, including but not limited to acromegaly
9.Opioid overdose or poly pharmacy drug overdose as the primary reason for admission to the ICU
10.Use of any of the following prokinetic medications during the current ICU admission and through Day 5: domperidone, cisapride, neostigmine, or opioid antagonists, including alvimopan, naloxone, naltrexone, or analogs of naloxone or naltrexone; erythromycin or azithromycin. [N.B., azithromycin is permitted for treatment of pulmonary infections up to 48 hours before randomization, but not thereafter through Day 5. Up to 2 doses of metoclopramide are permitted, provided that drug is not administered within 10 hours of the first dose of study drug or at any time through Day 5. If a patient receives metoclopramide during the screening period, a radiologic examination must confirm that the feeding tube remains visible in the stomach after the final dose of drug during screening and prior to the start of baseline gastric emptying measurements and has not migrated to the duodenum. Use of clarithromycin for any indication is not excluded.]
Propofol must be discontinued before screening. However, its use may be permitted under special conditions subsequent to the first dose of study drug but not in excess of 12 hours cumulative administration over the 5-day study period. (See Section 3.4.10.2)
11.Known allergy or intolerance to metoclopramide or paracetamol
12.Patient’s clinical condition is deteriorating rapidly, or the Investigator does not consider there to be a reasonable expectation that the patient will complete the study
13.Childs C cirrhosis or ALT ≥ 1000 U/L
14.Advanced or end-stage malignancy
15.Patient has participated in another study involving an investigational drug or device within the 30 days before study drug administration, or patient has previously participated in a study with ulimorelin
16.Patient has any other condition that in the opinion of the Investigator precludes participation in the trial, including limited access for required blood samples
17.Patient’s care is unlikely to comply with the protocol-defined procedures, as determined by the Investigator

1.Imposibilidad de obtener el consentimiento informado por escrito del paciente o de su representante legal para participar en el estudio
2.Uso previo, durante el presente ingreso en la UCI, de nutrición parenteral o alimentación trófica, definida como una prescripción de recibir ≤ 20 ml/hora de alimentación enteral durante más de 24 horas antes de la selección. [Nota: podrá iniciarse nutrición parenteral después de la aleatorización, siempre que la nutrición complementaria se coordine con los objetivos calóricos y proteicos del PTV y se reduzca a medida que se aumente la nutrición enteral]
3.Peso del paciente que excede de 150 kg antes del ingreso en la UCI
4.Sospecha o confirmación de oclusión, perforación o escape intestinal
5.Antecedente de cirugía esofágica o gástrica antes del ingreso hospitalario actual o durante el mismo
6.Uso de alguno de los siguientes procinéticos durante el ingreso actual en la UCI: domperidona, cisaprida, neostigmina o antagonistas opiáceos, incluidos alvimopán, naloxona, naltrexona o análogos de la naloxona o la naltrexona; eritromicina o azitromicina. (NOTA: se permite el uso de azitromicina para el tratamiento de infecciones pulmonares hasta 48 horas antes de la aleatorización, pero no a partir de entonces hasta el día 5. Se permite un máximo de 2 dosis de metoclopramida, siempre y cuando el fármaco no se administre en las 10 horas anteriores a la primera dosis del fármaco del estudio ni en ningún momento hasta el día 5. Si un paciente recibe metoclopramida durante el período de selección, un estudio radiológico debe confirmar que la sonda de alimentación sigue siendo visible en el estómago después de la última dosis del fármaco durante la selección y hasta antes del comienzo de las determinaciones basales del vaciamiento gástrico y que no se ha desplazado al duodeno. Se permite el uso de claritromicina para cualquier indicación. Debe suspenderse el propofol antes de la selección. Sin embargo, en circunstancias especiales se podrá permitir su uso después de la primera dosis del fármaco del estudio, pero sin que pueda suponer más de 12 horas de administración durante todo el periodo de 5 días.)
7.Estado clínico del paciente en rápido deterioro o el investigador considera que no existe una esperanza razonable de que el paciente vaya a terminar el estudio
8.Cirrosis (Child C) o ALT ≥ 1000 U/l

E.5 End points

E.5.1

Primary end point(s)

Primary Efficacy Endpoint:
The daily average (mean) percentage of target daily protein received through enteral nutrition by mechanically ventilated and tube-fed patients with EFI, Days 1 through 5.

Proteínas (g) recibidas con la nutrición enteral durante el período del tratamiento como porcentaje del objetivo proteico diario deseado.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1 to Day 5

Dias 1 al 5

E.5.2

Secondary end point(s)

Secondary Efficacy Endpoint: The daily average (mean) percentage of target daily calories received through enteral nutrition by mechanically ventilated and tube-fed patients with EFI, Days 1 through 5

Calorías (kcal) recibidas con la nutrición enteral durante el período del tratamiento como porcentaje del objetivo calórico diario deseado

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 1 through Day 5

Dias 1 al 5

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

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

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Metoclopramida

Metoclopramide

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

Netherlands

Spain

United States

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

LVLS

última visita ultimo paciente

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:

115

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

ICU patients

Pacientes ingresados en UCI

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

105

F.4.2.2

In the whole clinical trial

120

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)

None

Ninguna

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

2016-08-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-06-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-03-09

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials