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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05195892

Collaborator

(none)

Enrollment

Location

Arms

8.9

Anticipated Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Treatment A Drug: Treatment B Drug: Treatment C	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single-center, Randomized, Open-label, Three-period Crossover Study to Investigate the Bioequivalence of Alpelisib Granule and Film-coated Tablet Formulation, and the Food Effect of Alpelisib Granule Formulation in Adult Healthy Volunteers

Actual Study Start Date :

Feb 3, 2022

Anticipated Primary Completion Date :

Nov 2, 2022

Anticipated Study Completion Date :

Nov 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Treatment A Single oral dose of alpelisib film-coated tablet at 50 mg in fed state Drug: Treatment B Single oral dose of alpelisib granule at 50 mg in fed state Drug: Treatment C Single oral dose of alpelisib granule at 50 mg in fasted state
Experimental: 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.	Drug: Treatment A Single oral dose of alpelisib film-coated tablet at 50 mg in fed state Drug: Treatment B Single oral dose of alpelisib granule at 50 mg in fed state Drug: Treatment C Single oral dose of alpelisib granule at 50 mg in fasted state
Experimental: 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.	Drug: Treatment A Single oral dose of alpelisib film-coated tablet at 50 mg in fed state Drug: Treatment B Single oral dose of alpelisib granule at 50 mg in fed state Drug: Treatment C Single oral dose of alpelisib granule at 50 mg in fasted state
Experimental: 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).	Drug: Treatment A Single oral dose of alpelisib film-coated tablet at 50 mg in fed state Drug: Treatment B Single oral dose of alpelisib granule at 50 mg in fed state Drug: Treatment C Single oral dose of alpelisib granule at 50 mg in fasted state
Experimental: 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).	Drug: Treatment A Single oral dose of alpelisib film-coated tablet at 50 mg in fed state Drug: Treatment B Single oral dose of alpelisib granule at 50 mg in fed state Drug: Treatment C Single oral dose of alpelisib granule at 50 mg in fasted state
Experimental: 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).	Drug: Treatment A Single oral dose of alpelisib film-coated tablet at 50 mg in fed state Drug: Treatment B Single oral dose of alpelisib granule at 50 mg in fed state Drug: Treatment C Single oral dose of alpelisib granule at 50 mg in fasted state

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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]
Blood samples will be collected at specified time points to compare Cmax of the granule formulation in the fed state (Treatment B) versus the granule formulation in the fasted state (Treatment C). PK parameters will be calculated using noncompartmental data analysis of plasma concentration-time data.
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]
Blood samples will be collected at specified time points to calculate AUC0-96 of alpelisib after a single oral dose of alpelisib film coated tablet formulation in fed state (Treatment A), after a single oral dose of alpelisib granule formulation in fed state (Treatment B), after a single oral dose of alpelisib granule formulation in fasted state (Treatment C). PK parameters will be calculated using noncompartmental data analysis of plasma concentration-time data

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).