Investigate Bioequivalence of Alpelisib Granule and Film-coated Tablet Formulation and the Food Effect of Alpelisib Granule Formulation in Adult Healthy Volunteers

NCT ID: NCT05195892

Last Updated: 2022-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-03

Study Completion Date

2022-11-09

Brief Summary

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The purpose of this study is to assess bioequivalence of the granule formulation of alpelisib as compared to the film-coated tablet formulation in healthy volunteers in the fed state. In addition, the food effect of the granule formulation will be investigated between the fed state and the fasted state.

Detailed Description

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This is a single-center, randomized, open-label, three-period six-sequence crossover study.

The study consists of a screening period followed by Periods 1, 2, and 3 and a safety follow-up. Randomization occurs at the beginning of Period 1, whereby every participant who passes the screening will be randomized to one of 6 sequences with 1:1:1:1:1:1 randomization ratio. Each sequence consists of a permutation of three treatments: A, B and C. The order of the sequence of the treatments (A, B, C) will be determined by randomization to the assigned sequence.

A total of 60 participants will be enrolled with approximately 10 participants per sequence, in order to obtain at least 48 evaluable participants for comparison of the granule formulation in fed status and the film-coated tablet formulation in fed status.

Conditions

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Healthy Volunteers

Keywords

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adult bioequivalence food effect three-period six sequence crossover alpelisib BYL719

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sequence 1

Participants will receive a single oral dose of alpelisib film-coated tablet at 50 mg in fed state (treatment A) in period 1 followed by a single oral dose of alpelisib granule at 50 mg in fed state (treatment B) in period 2 and a single oral dose of alpelisib granule at 50 mg in fasted state (treatment C) in period 3.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Treatment B

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fed state

Treatment C

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fasted state

Sequence 2

Participants will receive a single oral dose of alpelisib granule at 50 mg in fed state (treatment B) in period 1 followed by a single oral dose of alpelisib granule at 50 mg in fasted state (treatment C) in period 2 followed by a single oral dose of alpelisib film-coated tablet at 50 mg in fed state (treatment A) in period 3.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Treatment B

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fed state

Treatment C

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fasted state

Sequence 3

Participants will receive a single oral dose of alpelisib granule at 50 mg in fasted state (treatment C) in period 1 followed by a single oral dose of alpelisib film-coated tablet at 50 mg in fed state (treatment A) in period 2 followed by a single oral dose of alpelisib granule at 50 mg in fed state (treatment B) in period 3.

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Treatment B

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fed state

Treatment C

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fasted state

Sequence 4

Participants will receive a single oral dose of alpelisib granule at 50 mg in fasted state (treatment C) in period 1 followed by a single oral dose of alpelisib granule at 50 mg in fed state (treatment B) in period 2 followed by a single oral dose of alpelisib film-coated tablet at 50 mg in fed state (treatment A).

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Treatment B

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fed state

Treatment C

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fasted state

Sequence 5

Participants will receive a single oral dose of alpelisib film-coated tablet at 50 mg in fed state (treatment A) in period 1 followed by a single oral dose of alpelisib granule at 50 mg in fasted state (treatment C) in period 2 followed by a single oral dose of alpelisib granule at 50 mg in fed state (treatment B).

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Treatment B

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fed state

Treatment C

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fasted state

Sequence 6

Participants will receive a single oral dose of alpelisib granule at 50 mg in fed state (treatment B) in period 1 followed by a single oral dose of alpelisib film-coated tablet at 50 mg in fed state (treatment A) in period 2 followed by a single oral dose of alpelisib granule at 50 mg in fasted state (treatment C).

Group Type EXPERIMENTAL

Treatment A

Intervention Type DRUG

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Treatment B

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fed state

Treatment C

Intervention Type DRUG

Single oral dose of alpelisib granule at 50 mg in fasted state

Interventions

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Treatment A

Single oral dose of alpelisib film-coated tablet at 50 mg in fed state

Intervention Type DRUG

Treatment B

Single oral dose of alpelisib granule at 50 mg in fed state

Intervention Type DRUG

Treatment C

Single oral dose of alpelisib granule at 50 mg in fasted state

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female participants 18 and 55 years of age
* Female participants must be postmenopausal or not of child bearing potential.
* Participants must weigh 50 kg - 120 kg and have BMI= 18.0-30.0 kg/m2
* Participants should be in good health as determined by no clinically significant findings from the medical history, physical examination, vital signs, and ECG.
* Participant must have laboratory values (including fasting plasma glucose and HgbA1C) within the reference range at the local laboratory
* At screening, and at baseline visit of each Period, participant has vital signs which are within the protocol defined ranges

Exclusion Criteria

* Women of childbearing potential
* Sexually active male participant with partner(s) of women of childbearing potential, UNLESS agree to comply with highly effective contraception AND use a condom
* Participant with
* significant illness, including infections, or hospitalization within the 30 days prior to dosing.
* diabetes mellitus or participants with fasting plasma glucose (FPG) levels \> 100 mg/dL or \>5.55 mmol/L.
* clinically significant risk of developing diabetes mellitus during the study
* Use of:
* tobacco products within 3 months prior to first dosing
* drug or alcohol abuse within 12 months prior to first dose
* alcohol within 48 hours prior to the dosing of each treatment period.
* any prescription or non-prescription, herbal medication, dietary supplements or vitamins during 14 days prior to dosing..
* History of :
* clinically significant hematologic, renal, endocrinologic, pulmonary, cardiovascular, hepatic, or allergic disease, medically documented. including uncontrolled hypertension, interstitial lung disease, or other causes of dyspnea, acute pancreatitis within 1 year of screening or past medical
* chronic pancreatitis.
* cardiac disease
* immunodeficiency diseases
* malignancy of any organ system carcinoma of the skin or in situ cervical cancer), within 5 years,
* erythema multiform (EM), Steven-Johnson-Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
* history or presence of
* any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.
* clinically significant ECG abnormalities or a family prolonged QT-interval syndrome.
* chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Belfast, Northern Ireland, United Kingdom

Site Status

Countries

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United Kingdom

References

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Burmeister Getz E, Niglis S, Papadimitriou A, Statelova M, Ren X, Nakhla K, Sharaby S, Tariq M, Garbuio L, Bakhsh S. Predicting and Confirming Bioequivalence of Alpelisib Oral Granules and Tablets for Patients With PIK3CA-Related Disorders. AAPS PharmSciTech. 2025 Apr 30;26(5):121. doi: 10.1208/s12249-025-03109-4.

Reference Type DERIVED
PMID: 40307580 (View on PubMed)

Other Identifiers

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CBYL719F12101

Identifier Type: -

Identifier Source: org_study_id