A Phase I Study to Evaluate the Taste of Belumosudil Oral Suspensions & Assess Relative Bioavailability

NCT04735822 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: KD025-1112020-003446-37
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, randomized, open-label, 2-part study in healthy male subjects to evaluate the taste profile of different belumosudil oral suspensions and the relative bioavailability of those chosen oral suspensions of belumosudil compared to oral tablets of belumosudil. Part 1 is an open-label, randomized single-period study of oral suspensions of belumosudil 40 mg/mL delivered in 6 different vehicles. Approximately 12 healthy male subjects, 2 subjects in each of 6 groups, will be administered a single dose of belumosudil 40 mg/mL in 6 different vehicles (Vehicles 1, 2, 3, 4, 5, and 6) in corresponding Regimens A, B, C, D, E, and F in different sequences of the 6 vehicles. All subjects will receive 1 dose of all belumosudil in all 6 vehicles which are as follows: ABFCED; BCADFE; CDBEAF; DECFBA; EFDACB; and FAEBDC. Part 2 is a single-center, open-label, randomized, 3-period design to assess the relative bioavailability of a selected belumosudil suspension formulation compared to the oral belumosudil. Tablet reference and the effect of food on the selected belumosudil suspension formulation in 18 healthy male subjects. Subjects will be randomized prior to the administration of the first dose of IMP to 1 of 6 treatment sequences (GHI, HIG, IGH, IHG, GIH and HGI), with 3 subjects assigned to each treatment sequence where: Regimen G--oral belumosudil 200 mg tablet (reference) with the subject fed; Regimen H--belumosudil powder 200 mg for oral suspension or belumosudil 200 mg oral suspension with the subject fasting; and Regimen I--belumosudil 200 mg powder for oral suspension or belumosudil 200 mg oral suspension with the subject fed.

Conditions

Healthy Volunteers

Keywords

Belumosudil; KD025; SLx-2119; ROCK inhibitor; Healthy male subjects

Outcome Measures

Primary Outcomes (2)

• Comparison of Taste/Palatability Questionnaire for Regimens B, C, D, E, F vs. Regimen A (Part 1 Only)

  Comparison of Taste/Palabability Questionnaire results of (1) Regimen B (belumosudil 400 mg/mL using Vehicle 2) vs. Regimen A (belumosudil 400 mg/mL using Vehicle 1); (2) Regimen C (belumosudil 400 mg/mL using Vehicle 3) vs. Regimen A; (3) Regimen D (belumosudil 40 mg/mL using Vehicle 4) vs. Regimen A; (4) Regimen E (belumosudil 40 mg/mL using Vehicle 5) vs. Regimen A; and (5) Regimen F (belumosudil 40 mg/mL using Vehicle 5) vs. Regimen A. The Taste/Probability Questionnaire assess smell, sweetness, bitterness, flavor, mouth feel/texture, grittiness, and aftertaste. Subjects rate each sense on a categorical scale ranging from extreme dislike to extreme like.

  Immediately after dosing

• Selection of Belumosudil Suspension Formulation for Part 2

  Selection of the belumosudil suspension formulation to be used in Part 2 of the study

  After administration of belumosudil 40 mg/mL with each of the 6 vehicles in the sequence assigned

Secondary Outcomes (21)

• Pharmacokinetics (Part 2 Only): Relative Bioavailability of Regimen I vs. Regimen G

  Up to 72 hours post-dose

• Pharmacokinetics (Part 2 Only): Determination of Tlag of Belumosudil 200 mg

  Up to 72 hours post-dose

• Pharmacokinetics (Part 2 Only): Determination of Tmax of Belumosudil 200 mg

  Up to 72 hours post-dose

• Pharmacokinetics (Part 2 Only): Determination of Cmax of Belumosudil 200 mg

  Up to 72 hours post-dose

• Pharmacokinetics (Part 2 Only): Determination of AUC(0-24) of Belumosudil 200 mg

  Up to 72 hours post-dose

Study Arms (12)

Part 1: Belumosudil Sequence ABFCED

EXPERIMENTAL

Subjects receive 1 dose of belumosudil 40 mg/mL in oral suspension in the following sequence: Regimen A (delivered by Vehicle 1); Regimen B (delivered by Vehicle 2); Regimen F (delivered by Vehicle 6); Regimen C (delivered by Vehicle 3); Regimen E (delivered by Vehicle 5); Regimen D (delivered by Vehicle 4);

Drug: Part 1: Belumosudil 40 mg/mL Sequence ABFCED

Part 1: Belumosudil Sequence BCADFE

EXPERIMENTAL

Subjects receive 1 dose of belumosudil 40 mg/mL in oral suspension in the following sequence: Regimen B (delivered by Vehicle 2); Regimen C (delivered by Vehicle 3); Regimen A (delivered by Vehicle 1); Regimen D (delivered by Vehicle 4); Regimen F (delivered by Vehicle 6); Regimen E (delivered by Vehicle 5)

Drug: Part 1: Belumosudil 40 mg/mL Sequence BCADFE

Part 1: Belumosudil Sequence CDBEAF

EXPERIMENTAL

Subjects receive 1 dose of belumosudil 40 mg/mL in oral suspension in the following sequence: Regimen C (delivered by Vehicle 3); Regimen D (delivered by Vehicle 4); Regimen B (delivered by Vehicle 2); Regimen E (delivered by Vehicle 6); Regimen A (delivered by Vehicle 1); Regimen F (delivered by Vehicle 6)

Drug: Part 1: Belumosudil 40 mg/mL Sequence CDBEAF

Part 1: Belumosudil Sequence DECFBA

EXPERIMENTAL

Subjects receive 1 dose of belumosudil 40 mg/mL in oral suspension in the following sequence: Regimen D (delivered by Vehicle 4); Regimen E (delivered by Vehicle 5); Regimen C (delivered by Vehicle 3); Regimen F (delivered by Vehicle 6); Regimen B (delivered by Vehicle 2); Regimen A (delivered by Vehicle 1)

Drug: Part 1: Belumosudil 40 mg/mL Sequence DECFBA

Part 1: Belumosudil Sequence EFDACB

EXPERIMENTAL

Subjects receive 1 dose of belumosudil 40 mg/mL in oral suspension in the following sequence: Regimen E (delivered by Vehicle 5); Regimen F (delivered by Vehicle 6); Regimen D (delivered by Vehicle 4); Regimen A (delivered by Vehicle 1); Regimen C (delivered by Vehicle 3); Regimen B (delivered by Vehicle 2)

Drug: Part 1: Belumosudil 40 mg/mL Sequence EFDACB

Part 1: Belumosudil Sequence FAEBDC

EXPERIMENTAL

Subjects receive 1 dose of belumosudil 40 mg/mL in oral suspension in the following sequence: Regimen F (delivered by Vehicle 6); Regimen A (delivered by Vehicle 1); Regimen E (delivered by Vehicle 5); Regimen B (delivered by Vehicle 2); Regimen D (delivered by Vehicle 4); Regimen C (delivered by Vehicle 3).

Drug: Part 1: Belumosudil 40 mg/mL Sequence FAEBDC

Part 2: Belumosudil Sequence GHI

EXPERIMENTAL

Subjects receive 1 dose in the following sequence; Regimen G (belumosudil 200 mg tablet fed); Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fasted); Regimen I (powder for oral suspension or oral suspension belumosudil 200 mg fed)

Drug: Part 2: Belumosudil 200 mg Sequence GHI

Part 2: Belumosudil Sequence HIG

EXPERIMENTAL

Subjects receive 1 dose in the following sequence: Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fasted); Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fed); Regimen G (belumosudil 200 mg tablet fed)

Drug: Part 2: Belumosudil 200 mg Sequence HIG

Part 2: Belumosudil Sequence IGH

EXPERIMENTAL

Subjects receive 1 dose in the following sequence: Regimen I (powder for oral suspension or oral suspension belumosudil 200 mg fed); Regimen G (belumosudil 200 mg tablet fed); Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fasted)

Drug: Part 2: Belumosudil 200 mg Sequence IGH

Part 2: Belumosudil Sequence IHG

EXPERIMENTAL

Subjects receive 1 dose in the following sequence: Regimen I (powder for oral suspension or oral suspension belumosudil 200 mg fed); Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fasted); Regimen G (belumosudil 200 mg tablet fed)

Drug: Part 2: Belumosudil 200 mg Sequence IHG

Part 2: Belumosudil Sequence GIH

EXPERIMENTAL

Subjects receive 1 dose in the following sequence: Regimen G (belumosudil 200 mg tablet fed); Regimen I (powder for oral suspension or oral suspension belumosudil 200 mg fed); Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fasted)

Drug: Part 2: Belumosudil 200 mg Sequence GIH

Part 2: Belumosudil Sequence HGI

EXPERIMENTAL

Subjects receive 1 dose in the following sequence: Regimen H (powder for oral suspension or oral suspension belumosudil 200 mg fasted); Regimen G (belumosudil 200 mg tablet); Regimen I (powder for oral suspension or oral suspension belumosudil 200 mg fed);

Drug: Part 2: Belumosudil 200 mg Sequence HGI

Interventions

Part 1: Belumosudil 40 mg/mL Sequence ABFCED DRUG

Oral suspension belumosudil 40 mg/mL in sequence Regimen A, then Regimen B, then Regimen F, then Regimen C, then Regimen E, then Regimen D

Also known as: KD025

Part 1: Belumosudil Sequence ABFCED

Part 1: Belumosudil 40 mg/mL Sequence BCADFE DRUG

Oral suspension belumosudil 40 mg/mL in sequence Regimen B, then Regimen C, then Regimen A, then Regimen D, then Regimen F, then Regimen E

Also known as: KD025

Part 1: Belumosudil Sequence BCADFE

Part 1: Belumosudil 40 mg/mL Sequence CDBEAF DRUG

Oral suspension belumosudil 40 mg/mL in sequence Regimen C, then Regimen D, then Regimen B, then Regimen E, then Regimen A, then Regimen F

Also known as: KD025

Part 1: Belumosudil Sequence CDBEAF

Part 1: Belumosudil 40 mg/mL Sequence DECFBA DRUG

Oral suspension of belumosudil 40 mg/mL in sequence Regimen D, then Regimen E, then Regimen C, then Regimen F, then Regimen B, then Regimen A

Also known as: KD025

Part 1: Belumosudil Sequence DECFBA

Part 1: Belumosudil 40 mg/mL Sequence EFDACB DRUG

Oral suspension of belumosudil 40 mg/mL in sequence Regimen E, then Regimen F, then Regimen D, then Regimen A, then Regimen C, then Regimen C

Also known as: KD025

Part 1: Belumosudil Sequence EFDACB

Part 1: Belumosudil 40 mg/mL Sequence FAEBDC DRUG

Oral suspension of belumosudil 40 mg/mL in sequence Regimen F, then Regimen A, then Regimen E, then Regimen B, then Regimen D, then Regimen C

Also known as: KD025

Part 1: Belumosudil Sequence FAEBDC

Part 2: Belumosudil 200 mg Sequence GHI DRUG

1 dose of belumosudil 200 mg in sequence Regimen G (tablet), then Regimen H (oral suspension; subject fasted), then Regimen I (oral suspension; subject fed)

Also known as: KD025

Part 2: Belumosudil Sequence GHI

Part 2: Belumosudil 200 mg Sequence HIG DRUG

1 dose of belumosudil 200 mg in sequence Regimen H (oral suspension; subject fasted), then Regimen I (oral suspension; subject fed), then Regimen G (tablet)

Also known as: KD025

Part 2: Belumosudil Sequence HIG

Part 2: Belumosudil 200 mg Sequence IGH DRUG

1 dose of belumosudil 200 mg in sequence Regimen I (oral suspension; subject fed), then Regimen G (tablet), then Regimen H (oral suspension, subject fasted)

Also known as: KD025

Part 2: Belumosudil Sequence IGH

Part 2: Belumosudil 200 mg Sequence IHG DRUG

1 dose of belumosudil 200 mg in sequence Regimen I (oral suspension; subject fed), then Regimen H (oral suspension; subject fasted), then Regimen G (tablet)

Also known as: KD025

Part 2: Belumosudil Sequence IHG

Part 2: Belumosudil 200 mg Sequence GIH DRUG

1 dose of belumosudil 200 mg in sequence Regimen G (tablet), then Regimen I (oral suspension; subject fed), then Regimen H (oral suspension; subject fasted)

Also known as: KD025

Part 2: Belumosudil Sequence GIH

Part 2: Belumosudil 200 mg Sequence HGI DRUG

1 dose of belumosudil 200 mg in sequence Regimen H (oral suspension; subject fasted), then Regimen G (tablet), then Regimen I (oral suspension; subject fed)

Also known as: KD025

Part 2: Belumosudil Sequence HGI

Eligibility Criteria

• Age: 18 Years - 55 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males
• Aged 18 to 55 years inclusive at the time of signing informed consent.
• Body mass index of 18.0 to 32.0 kg/m\^2 at screening
• Body weight ≥ 50 kg at screening
• Must be willing and able to communicate and participate in the entire study
• Must provide written informed consent
• Must agree to adhere to the contraception requirements

You may not qualify if:

• Subjects who have received any IMP in a previous clinical research study within the 90 days prior to Day 1 (Part 2 only)
• Subjects who are or are immediate family members of a study site or sponsor employee
• Subjects who have previously been administered IMP in Part 2 of this study. Subjects who have taken part in Part 1 are permitted to take part in Part 2
• Evidence of current SARS-CoV-2 infection
• Clinically significant history or presence of acute or chronic bacterial, fungal, or viral infection (e.g., pneumonia, septicemia) within the 3 months or 90 days prior to screening
• Any subject with clinically significant symptoms of COVID-19 in the last 4 weeks, including but not limited to fever, new and persistent cough, breathlessness or loss of taste or smell, as per the judgement of the investigator
• Known or suspected malignancy, autoimmune disorder, or any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the participant's immune status or any factor that would predispose participants to develop infection (e.g., open skin lesions, recurrent issues related to poor dentition, perianal fissures, history of splenectomy, primary immunodeficiency)
• History of any drug or alcohol abuse in the past 2 years
• Regular alcohol consumption in males \> 21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirits, 1.5 to 2 units = 125 mL glass of wine, depending on type)
• A confirmed positive alcohol breath test at screening or admission
• Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
• Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
• Subjects with pregnant or lactating partners
• Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator or delegate at screening
• Clinically significant abnormal clinical chemistry, hematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed.

Sponsors & Collaborators

• Kadmon Corporation, LLC: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences

Nottingham, England, NG11 6J5, United Kingdom

Location

MeSH Terms

Interventions

KD025

Study Officials

• Nand Singh, BSc, MD, DPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Part 1: Single center, open-label, randomized, 6-arm design to assess the taste profile of different novel belumosudil in bottle formations in 12 healthy male subjects. Part 2: Single center, open-label, randomized, 3-arm, design to assess the relative bioavailability of a selected belumosudil suspension formulation compared to the oral belumosudil tablet reference and the effect of food on the selected belumosudil suspension formulation in 18 health male subjects

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: February 3, 2021
• Study Start: October 26, 2020
• Primary Completion: September 3, 2021
• Study Completion: September 3, 2021
• Last Updated: May 11, 2022

Record last verified: 2022-05

Locations

GB (1)