A Trial to Evaluate the Impact of C21 on the Exposure of 4 Substrates in Healthy Volunteers

NCT05830799 | Completed Phase 1 Results

• 1 other identifier: VP-C21-012
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-centre, open-label, fixed-sequence trial to evaluate the impact of C21 on the exposure of CYP1A2, CYP2C9, CYP3A4 and P-gp substrates in healthy volunteers.

Conditions

Drug Interaction

Outcome Measures

Primary Outcomes (16)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Caffeine and Paraxanthine (Cmax)

  Maximum observed concentration (Cmax) for caffeine and its metabolite paraxanthine.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Caffeine and Paraxanthine (Tmax)

  Time of occurrence of Cmax (Tmax) for caffeine and its metabolite paraxanthine.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Caffeine and Paraxanthine (AUC0-last)

  Area under the plasma concentration vs. time curve from 0 to time of last measurable plasma concentration (AUC0-last) for caffeine and its metabolite paraxanthine.

  Day 2 to day 19

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Caffeine and Paraxanthine (AUC0-inf)

  Area under the plasma concentration vs. time curve from 0 to infinity (AUC0-inf) for caffeine and its metabolite paraxanthine.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Tolbutamide and 4-hydroxy-tolbutamide and Carboxy-tolbutamide (Cmax)

  Maximum observed concentration (Cmax) for Tolbutamide and its metabolites 4-hydroxy-tolbutamide and carboxy-tolbutamide.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Tolbutamide and 4-hydroxy-tolbutamide and Carboxy-tolbutamide (Tmax)

  Time of occurrence of Cmax (Tmax) for Tolbutamide and its metabolites 4-hydroxy-tolbutamide and carboxy-tolbutamide.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Tolbutamide and 4-hydroxy-tolbutamide and Carboxy-tolbutamide (AUC0-last)

  Area under the plasma concentration vs. time curve from 0 to time of last measurable plasma concentration (AUC0-last) for Tolbutamide and its metabolites 4-hydroxy-tolbutamide and carboxy-tolbutamide.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Tolbutamide and 4-hydroxy-tolbutamide and Carboxy-tolbutamide (AUC0-inf)

  Area under the plasma concentration vs. time curve from 0 to infinity (AUC0-inf) for Tolbutamide and its metabolites 4-hydroxy-tolbutamide and carboxy-tolbutamide.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Midazolam and 1-hydroxy-midazolam (Cmax)

  Maximum observed concentration (Cmax) for midazolam and its metabolite 1-hydroxy-midazolam.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Midazolam and 1-hydroxy-midazolam (Tmax)

  Time of occurrence of Cmax (Tmax) for midazolam and its metabolite 1-hydroxy-midazolam.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Midazolam and 1-hydroxy-midazolam (AUC0-last)

  Area under the plasma concentration vs. time curve from 0 to time of last measurable plasma concentration (AUC0-last) for midazolam and its metabolite 1-hydroxy-midazolam.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Midazolam and 1-hydroxy-midazolam (AUC0-inf)

  Area under the plasma concentration vs. time curve from 0 to to infinity (AUC0-inf) for midazolam and its metabolite 1-hydroxy-midazolam.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24 hours post dose at Day 2 (period 1), Day 5 (period 2) and Day 18 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Nintedanib and BIBF 1202 (Cmax)

  Maximum observed concentration (Cmax) for nintedanib and its metabolite BIBF 1202.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 hours post dose at Day 1 (period 1), Day 4 (period 2) and Day 17 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Nintedanib and BIBF 1202 (Tmax)

  Time of occurrence of Cmax (Tmax) for nintedanib and its metabolite BIBF 1202.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 hours post dose at Day 1 (period 1), Day 4 (period 2) and Day 17 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Nintedanib and BIBF 1202 (AUC0-last)

  Area under the plasma concentration vs. time curve from 0 to time of last measurable plasma concentration (AUC0-last) for nintedanib and its metabolite BIBF 1202.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 hours post dose at Day 1 (period 1), Day 4 (period 2) and Day 17 (period 3)

• To Evaluate the Impact of C21 on the Pharmacokinetics (PK) of Nintedanib and BIBF 1202 (AUC0-inf)

  Area under the plasma concentration vs. time curve from 0 to infinity (AUC0-inf) for nintedanib and its metabolite BIBF 1202.

  Pre-dose and 0:15, 0:30, 0:45, 1, 1:30, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48 hours post dose at Day 1 (period 1), Day 4 (period 2) and Day 17 (period 3)

Secondary Outcomes (8)

• To Evaluate the Pharmacokinetics (PK) of C21 and M1 (Cmax)

  Day 17

• To Evaluate the Pharmacokinetics (PK) of C21 and M1 (Tmax)

  Day 17

• To Evaluate the Pharmacokinetics (PK) of C21 and M1 (AUC0-last)

  Day 17

• To Evaluate the Pharmacokinetics (PK) of C21 and M1 (AUC0-tau)

  Day 17

• To Evaluate the Safety of C21 (AEs)

  From signing ICF to Day 25

Study Arms (1)

Experimental: C21

EXPERIMENTAL

C21, single dose, oral administration twice daily, for 15 days

Drug: Drug Drug Interaction

Interventions

Drug Drug Interaction DRUG

The intervention phase consists of 3 periods: in period 1, the pharmacokinetics (PK) of all substrates will be evaluated in the absence of C21, in period 2, a potential inhibitory effect of C21 on the substrates be evaluated, and in period 3, the net effect of potential C21-mediated induction and inhibition on the substrates will be evaluated

Also known as: Caffeine, Koffein Meda, Tolbutamide, Tolbutamide CF, Midazolam, Midazolam APL, Nintedanib, Ofev

Experimental: C21

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give written informed consent for participation in the trial.
• Healthy male, or healthy female subject of non-childbearing potential, aged 18 to 60 years, inclusive.
• Body mass index ≥ 18.5 and ≤ 30.0 kg/m2 at the time of the screening visit.
• Medically healthy subject without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of the screening visit, as judged by the Investigator.
• Women of non-childbearing potential, i.e. pre-menopausal females who have undergone any of the following surgical procedures; hysterectomy, bilateral salpingectomy or bilateral oophorectomy, or who are post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone \[FSH\] \>25 IU/L is confirmatory).

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the trial, or influence the results or the subject's ability to participate in the trial.
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
• Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
• Any planned major surgery within the duration of the trial.
• Subjects who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
• Any positive result at the screening visit for serum hepatitis B surface antigen, hepatitis C antibodies and/or human immunodeficiency virus (HIV).
• After 10 minutes supine rest at the screening visit, any vital signs values outside the following ranges:
• Systolic blood pressure: \<90 or \>140 mmHg, or
• Diastolic blood pressure \<50 or \>90 mmHg, or
• Pulse \<40 or \>90 bpm
• Prolonged QTcF (\>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the screening visit, as judged by the Investigator.
• CYP2C9 genotype hetero- or homozygous for CYP2C9\*2 (Arg144Cys) and/or CYP2C9\*3 (Ile359Leu) variant alleles associated with altered CYP2C9 activity and tolbutamide metabolism \[14\], sampled at the screening visit.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to any of the IMPs.
• Regular use of any prescribed or non-prescribed medications, including antacids, analgesics, herbal remedies, e.g. St. John's wort, vitamins and minerals, within 2 weeks prior to the first administration of IMP, except occasional intake of paracetamol (maximum 2000 mg/day and not exceeding 3000 mg/week), as well as nasal decongestants without cortisone, antihistamine or anticholinergics for a maximum of 10 days, at the discretion of the Investigator.
• Planned treatment or treatment with another investigational drug within 3 months prior to Day -1. Subjects consented and screened but not dosed in previous phase 1 studies are not to be excluded.

Sponsors & Collaborators

• Vicore Pharma AB: lead

Study Sites (1)

CTC Clinical Trial Consultants AB

Uppsala, SE-752 37, Sweden

Location

MeSH Terms

Interventions

Drug Interactions; Caffeine; Tolbutamide; Midazolam; nintedanib

Intervention Hierarchy (Ancestors)

Pharmacological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena; Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Benzodiazepines; Benzazepines

Results Point of Contact

• Title: Cecilia Ganslandt, MD, MSc
• Organization: Vicore Pharma AB

info@vicorepharma.com

+46 31788 05 60

Study Officials

• Björn Schultze, MD

  CTC Clinical Trial Consultants AB

  PRINCIPAL INVESTIGATOR

• Måns Jergil, PhD

  CTC Clinical Trial Consultants AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, one group

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 26, 2023
• Study Start: March 29, 2023
• Primary Completion: May 11, 2023
• Study Completion: May 11, 2023
• Last Updated: January 3, 2025
• Results First Posted: January 3, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)