Clinical Trial Results:
Effect of the moderate CYP3A4-inhibitor erythromycin on the pharmacokinetics of palbociclib
Summary
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EudraCT number |
2018-004032-29 |
Trial protocol |
NL |
Global end of trial date |
10 May 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Jul 2022
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First version publication date |
24 Jul 2022
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Other versions |
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Summary report(s) |
Publication CLINICAL PHARMACOLOGY & THERAPEUTICS: Effects of the Moderate CYP3A4 Inhibitor Erythromycin on the Pharmacokinetics of Palbociclib |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M18CYP
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
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Sponsor organisation address |
Plesmanlaan 121, Amsterdam, Netherlands,
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Public contact |
Neeltje Steeghs, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, n.steeghs@nki.nl
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Scientific contact |
Neeltje Steeghs, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, n.steeghs@nki.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Jul 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 May 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
10 May 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this trial is to study the effect of the moderate CYP3A4 inhibitor erythromycin on the pharmacokinetics of palbociclib, measured as AUC0-24h, Cmax and Cmin.
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Protection of trial subjects |
Theoretically, the concomitant administration of palbociclib with erythromycin could lead to higher palbociclib exposure and thus give an increased risk of toxicities. However, the duration of this intervention is short (7 days). Although erythromycin rarely gives toxicities, this is a minor risk for patients. Since erythromycin could prolong the QTc interval, an ECG will be performed at screening. Patients with a prolonged QTc interval will be excluded.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
01 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 12
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Worldwide total number of subjects |
12
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EEA total number of subjects |
12
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
Pre-assignment
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Screening details |
Patients with histological or cytological proof of cancer with an indicationfor treatment with palbociclib (i.e., advanced breast cancer) at the standard dose of 125 mg q.d. were eligible for inclusion. Further inclusion criteria were aged ≥18 years, World Health Organization performance status of 0, 1, or 2, and adequate organ function. | |||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm A | |||||||||||||||
Arm description |
start with either palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.) and then crossover to palbociclib monotherapy 125 mg q.d. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
palbociclib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients were randomized to start with either palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.) and then crossover to palbociclib monotherapy 125 mg q.d.
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Investigational medicinal product name |
Erythromycin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients were randomized to start with either palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.) and then crossover to palbociclib monotherapy 125 mg q.d.
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Arm title
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Arm B | |||||||||||||||
Arm description |
Start with palbociclib monotherapy 125 mg q.d. and then crossover to palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
palbociclib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Start with palbociclib monotherapy 125 mg q.d. and then crossover to palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.)
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Investigational medicinal product name |
Erythromycin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Start with palbociclib monotherapy 125 mg q.d. and then crossover to palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.)
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End points reporting groups
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Reporting group title |
Arm A
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Reporting group description |
start with either palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.) and then crossover to palbociclib monotherapy 125 mg q.d. | ||
Reporting group title |
Arm B
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Reporting group description |
Start with palbociclib monotherapy 125 mg q.d. and then crossover to palbociclib 125 mg q.d. combined with erythromycin 500 mg three times daily (t.i.d.) |
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End point title |
Pharmacokinetics [1] | ||||||||||||
End point description |
To study the effect of the moderate CYP3A4 inhibitor erythromycin on the pharmacokinetics of palbociclib, measured as AUC0-24h, Cmax and Cmin.
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End point type |
Primary
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End point timeframe |
At Day 7 and Day 21 , patients were admitted and blood samples were collected for pharmacokinetic analyses. Timepoints were before dosing (directly before ingestion of palbociclib) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 24 hrs post dosing
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: See table 2 of publication attached |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Adverse events should be collected beginning from the time the patient starts the study treatment (Day 1) and ending with end of the study (Day 21).
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Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
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Dictionary name |
CTC | ||
Dictionary version |
5.0
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Frequency threshold for reporting non-serious adverse events: 1% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: See table 3 of publication attached. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Jan 2019 |
Erasmus Medical Center added as trial center |
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08 Dec 2020 |
Change # evaluable patients to 11 patients. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |