Clinical Trials Register

Summary
EudraCT Number:	2021-003805-23
Sponsor's Protocol Code Number:	A8081069
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2021-08-12
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2021-003805-23

A.3

Full title of the trial

A PHASE 1, OPEN LABEL, CROSSOVER STUDY TO EVALUATE PALATABILITY AND RELATIVE BIOAVAILABILITY OF TWO PEDIATRIC MICROSPHERE FORMULATIONS OF CRIZOTINIB IN HEALTHY PARTICIPANTS

A.3.1

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

Evaluate Taste and Relative Bioavailability of Two Microsphere Formulations of Crizotinib in Healthy Participants

A.4.1

Sponsor's protocol code number

A8081069

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03978143

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/036/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer, 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	Pfizer, 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	Pfizer, Inc.
B.5.2	Functional name of contact point	Clinical Trials.gov Call center
B.5.3	Address:
B.5.3.1	Street Address	235 E 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	10017
B.5.3.4	Country	United States
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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	Yes
D.2.1.1.1	Trade name	Xalkori
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
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	Xalkori
D.3.2	Product code	PF-02341066
D.3.4	Pharmaceutical form	Granules
D.3.4.1	Specific paediatric formulation	Yes
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	Crizotinib
D.3.9.1	CAS number	877399-52-5
D.3.9.2	Current sponsor code	PF-02341066
D.3.9.3	Other descriptive name	cMS1
D.3.9.4	EV Substance Code	SUB32267
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	250
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Crizotinib
D.3.9.1	CAS number	877399-52-5
D.3.9.2	Current sponsor code	PF-02341066
D.3.9.3	Other descriptive name	cMS2
D.3.9.4	EV Substance Code	SUB32267
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	250
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	Xalkori
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
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	Xalkori
D.3.2	Product code	PF-02341066
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	Yes
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	Crizotinib
D.3.9.1	CAS number	877399-52-5
D.3.9.2	Current sponsor code	PF-02341066
D.3.9.4	EV Substance Code	SUB32267
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	250
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: 3
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	Xalkori
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Europe MA EEIG
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	Xalkori
D.3.2	Product code	PF-02341066
D.3.4	Pharmaceutical form	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	Crizotinib
D.3.9.1	CAS number	877399-52-5
D.3.9.2	Current sponsor code	PF-02341066
D.3.9.4	EV Substance Code	SUB32267
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	250
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

This study was conducted in healthy subjects and it is required that all trial participants don’t have any medical condition.

E.1.1.1

Medical condition in easily understood language

None

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Pharmacokinetics: To estimate the relative bioavailability of 2 new crizotinib formulations (coated microsphere 1 {cMS1} and coated microsphere 2 {cMS2}) to the commercially available crizotinib formulated capsule (FC) at a single 250 mg dose administered under fasted conditions in adult healthy participants.
Taste: To evaluate the palatability of crizotinib cMS1 and cMS2 formulations of 250 mg dose in comparison with the crizotinib oral solution (OS) of 250 mg dose in adult healthy participants.

E.2.2

Secondary objectives of the trial

Safety: To assess the safety and tolerability of crizotinib 250 mg single doses in 4 different formulations (cMS1, cMS2, FC and OS) when given fasted, with high fat(HF) meal or with the proton pump inhibitor(PPI), esomeprazole, in adult healthy participants.

Pharmacokinetics: To explore the effect of food on the PK of cMS1 and cMS2.
To explore the effect of esomeprazole on the PK of cMS1 and cMS2.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests.

- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

- Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

E.4

Principal exclusion criteria

- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

- Any condition possibly affecting drug absorption (eg, gastrectomy, gastric or intestinal bypass surgery, cholecystectomy).

- Any condition possibly affecting the ability to taste (eg, dysgeusia, respiratory infection).

- Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever was longer) prior to the first dose of crizotinib.

- Participants with history of known sensitivity to esomeprazole or substituted benzimidazoles.

- Previous administration with an investigational product within 30 days or 5 half-lives preceding the first dose of crizotinib (whichever was longer).

- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.

E.5 End points

E.5.1

Primary end point(s)

Timepoint: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours post-dose after fasting administration of cMS1, cMS2 and capsule crizotinib

Area Under the Curve From Time Zero to Extrapolated Infinite Time

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

Maximum Observed Plasma Concentration (Cmax)

Timepoint: 1 (immediately after dosing), 5, 10, and 20 minutes after fasting administration of cMS1, cMS2 and OS crizotinib

•taste questionnaire score of overall liking of drug formulation

•taste questionnaire score of bitterness of drug formulation

•taste questionnaire score of mouth feel from drug formulation

•taste questionnaire score of tongue/mouth burn from drug formulation

•taste questionnaire score of throat burn from drug formulation

E.5.1.1

Timepoint(s) of evaluation of this end point

0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours post-dose after fasting administration of cMS1, cMS2 and capsule crizotinib

1 (immediately after dosing), 5, 10, and 20 minutes after fasting administration of cMS1, cMS2 and OS crizotinib

E.5.2

Secondary end point(s)

Timepoint: From screening to the end of study (safety)

Number of subjects and percentage of subjects reporting abnormal safety Laboratory tests, abnormal ECGs, abnormal vital signs and AEs

Timepoint: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours after administration of cMS1, cMS2 with and without food;
Timepoint: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours administration of cMS1, cMS2 after
esomeprazole dose; capsule dosing

AUCinf

AUClast

Cmax

cMS1, cMS2 with and without food; cMS1, cMS2 after esomeprazole dose; Capsule dosing

Time for Cmax (Tmax)

Terminal half-life (t1/2)

Apparent oral clearance (CL/F)

Apparent volume of distribution (Vz/F)

E.5.2.1

Timepoint(s) of evaluation of this end point

From screening to the end of study (safety)

Timepoint: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours after administration of cMS1, cMS2 with and without food;
Timepoint: 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, and 96 hours administration of cMS1, cMS2 after
esomeprazole dose; capsule dosing

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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

Bioavailability

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Relative bioavailability

E.7.2

Therapeutic exploratory (Phase II)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

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

different formulation

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

Yes

E.8.4

Will this trial be conducted at multiple sites globally?

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

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.8.9.2

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)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

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)

None

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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