A Study to Evaluate the Effect of High Fat Meal on Cabotegravir

NCT02799264 | Completed Phase 1

• 1 other identifier: 205696
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Cabotegravir is being developed for the treatment of human immunodeficiency virus (HIV) 1 infection. Specifically, it is being developed as a component of a 2-drug maintenance regimen (post-induction of viral suppression) that includes rilpivirine. Rilpivirine requires food for optimal absorption; therefore the recommended intake of cabotegravir in the planned Phase 3 treatment studies is with food regardless of fat or calorie content, when administered along with rilpivirine. This is a single-center, randomized, open-label, two-way crossover study in healthy adult subjects to assess the effect of a high fat meal on the single dose pharmacokinetics of CAB 30 mg. Approximately, 24 subjects will be enrolled in the study and will be screened for 30 days. Twelve subjects with at least 10 hours of fasting will be randomized to receive a single dose of cabotegravir orally (Schedule 'A'). The remaining 12 subjects will receive a single dose of cabotegravir orally along with high fat meal (Schedule 'B'). After 15 days, the subjects earlier undergoing 'Schedule A' will be switched to 'Schedule B' and those undergoing 'Schedule B' will undergo 'Schedule A'. All the subjects will be followed up to 30 days from the day of receiving first dose of cabotegravir to evaluate the effect of a high fat meal on the pharmacokinetics of cabotegravir.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

fasted; healthy volunteers; cabotegravir; high fat; pharmacokinetics; randomized; Phase I; two way crossover

Outcome Measures

Primary Outcomes (4)

• Area under the concentration time curve from time zero (pre dose) extrapolated to infinite time of cabotegravir

  AUC (0 infinity\[inf\]) is defined as the area under cabotegravir plasma concentration time curve from time zero (pre dose) extrapolated to infinite time.

  Pre dose, 0.5 hour (h), 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on Day(D) 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Area under the concentration time curve from time zero (pre dose) to last time of quantifiable concentration of cabotegravir

  AUC (0-t) is defined as area under cabotegravir plasma concentration time curve from time zero (pre dose) to the last time of quantifiable concentration.

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Maximum observed plasma concentration of cabotegravir

  Cmax is defined as the maximum observed plasma concentration of cabotegravir.

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Concentration of cabotegravir at 24 hours post dose (C24)

  C24 is defined as the plasma concentration at 24 hours after administration of cabotegravir.

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

Secondary Outcomes (13)

• Plasma terminal phase half life of cabotegravir

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Lag time before observation of cabotegravir concentration in sampled matrix

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Time of occurrence of maximum observed plasma concentration of cabotegravir

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Percentage of area under the concentration time curve of cabotegravir from time zero extrapolated to infinite time obtained by extrapolation

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

• Time of last measurable concentration of cabotegravir

  Pre dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h post dose on D 1, D 2, D 3, D 4, D 6, D 8 each for Period 1 and Period 2

Study Arms (2)

Cabotegravir 30 mg: Sequence AB (fasted followed by fed)

EXPERIMENTAL

There will be two administration periods with 14 days of wash out. In Period 1, eligible subjects will receive a single tablet of cabotegravir 30 mg,(micronized 500 mg core weight) orally under fasted condition with at least 10 hours of prior fast. In Period 2, eligible subjects will receive single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally following a high fat meal. Blood samples will be withdrawn from subjects prior to dosing and upto 8 days after the last dose of cabotegravir.

Drug: Cabotegravir 30 mg

Cabotegravir 30 mg: Sequence BA (fed followed by fasted)

EXPERIMENTAL

There will be two administration periods with 14 days of wash out. In Period 1, eligible subjects will receive single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally following a high fat meal. In Period 2, eligible subjects will receive a single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally under fasted condition with at least 10 hours of prior fast. Blood samples will be withdrawn from subjects prior to dosing and upto 8 days after the last dose of cabotegravir.

Drug: Cabotegravir 30 mg

Interventions

Cabotegravir 30 mg DRUG

Cabotegravir (GSK1265744B ) is available as white to almost white, oval shaped, film coated tablet, of weight 515 mg. The tablet contains micronized cabotegravir, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, and magnesium stearate. Each tablet is equivalent to 30 mg cabotegravir and needs to be taken orally with 240 mL of water. Cabotegravir tablet will be administered to subjects either in fasting condition or following a high fat meal.

Cabotegravir 30 mg: Sequence AB (fasted followed by fed); Cabotegravir 30 mg: Sequence BA (fed followed by fasted)

Eligibility Criteria

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

You may qualify if:

• An eligible subject should be between 18 to 65 years of age inclusive, at the time of signing the informed consent
• Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

You may not qualify if:

• Body weight \>= 50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per squared meter (kg/m\^2) (inclusive).
• Male or female subjects. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum or urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:
• Non reproductive potential defined as:
• Pre menopausal females with one of the following:
• Documented tubal ligation
• Documented hysteroscopic tubal occlusion procedure with follow up confirmation of bilateral tubal occlusion
• Hysterectomy
• Documented bilateral oophorectomy
• OR has only same sex partners, when this is her preferred and usual lifestyle Post menopausal is defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post menopausal status prior to study enrolment
• Reproductive potential and agrees to follow one of the options listed in the modified list of highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) from 30 days prior to the first dose of the study medication and until after the last dose of the study medication and completion of the follow up visit. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception
• Capable of giving signed informed consent that includes compliance with the requirements and restrictions listed in the consent form and in the protocol
• Alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin \<=1.5x Upper Limit of Normal (ULN ) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of clinically significant cardiovascular disease including:
• Evidence of previous myocardial infarction (pathologic Q waves, S T segment changes \[except early repolarization\])

Sponsors & Collaborators

• ViiV Healthcare: lead
• Glaxosmithkline/Quintiles: collaborator

Study Sites (1)

GSK Investigational Site

Overland Park, Kansas, 66211, United States

Location

Related Publications (1)

• Patel P, Ford SL, Lou Y, Bakshi K, Tenorio AR, Zhang Z, Pan R, Spreen W. Effect of a High-Fat Meal on the Pharmacokinetics of the HIV Integrase Inhibitor Cabotegravir. Clin Pharmacol Drug Dev. 2019 May;8(4):443-448. doi: 10.1002/cpdd.620. Epub 2018 Sep 19.

  PMID: 30230694 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

cabotegravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  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: June 9, 2016
• First Posted: June 14, 2016
• Study Start: June 1, 2016
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: January 13, 2017

Record last verified: 2017-01

Locations

US (1)