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

NCT05195892 | Completed Phase 1

• 1 other identifier: CBYL719F12101
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum concentration (Cmax) of alpelisib for Treatment A and Treatment B

  Blood samples will be collected at specified time points to compare Cmax of the test formulation (Treatment B: granule formulation in fed state) versus the reference formulation (Treatment A: the film-coated tablet formulation in fed state). PK parameters will be calculated using noncompartmental data analysis of plasma concentration-time data

  Period 1, 2 and 3 at pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12. 24, 48, 72 and 96 hours post-dose

Secondary Outcomes (2)

• Maximum concentration (Cmax) of alpelisib for Treatment B and Treatment C

  Period 1, 2 and 3 at pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12. 24, 48, 72 and 96 hours post-dose

• Area under plasma concentration time curve (AUC) from zero to 96 hours post dose of alpelisib for Treatment A, Treatment B and Treatment C

  Period 1, 2 and 3 at pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12. 24, 48, 72 and 96 hours post-dose

Study Arms (6)

Sequence 1

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Sequence 2

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Sequence 3

EXPERIMENTAL

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.

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Sequence 4

EXPERIMENTAL

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).

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Sequence 5

EXPERIMENTAL

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).

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Sequence 6

EXPERIMENTAL

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).

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Interventions

Treatment A DRUG

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

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Treatment B DRUG

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

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Treatment C DRUG

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

Sequence 1; Sequence 2; Sequence 3; Sequence 4; Sequence 5; Sequence 6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Belfast, Northern Ireland, BT9 6AD, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40307580 DERIVED

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: January 19, 2022
• Study Start: February 3, 2022
• Primary Completion: November 9, 2022
• Study Completion: November 9, 2022
• Last Updated: December 28, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)