Evaluation of Vamorolone CYP3A4 Induction on Midazolam (a Sensitive CYP 3A4 Substrate) Pharmacokinetics

NCT06689527 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: SNT-I-VAM-0252024-513845-36-00
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to investigate how vamorolone affects the CYP3A4 enzyme in humans by measuring the pharmacokinetics of midazolam and its metabolite, 1'-hydroxymidazolam, in healthy subjects. The pharmacokinetics of midazolam were measured on Day 1 and then on Day 14 to investigate the potential interaction between the two compounds. The safety and the tolerability was also investigated.

Conditions

Drug Interaction

Keywords

Drug-Drug-Interaction Study

Outcome Measures

Primary Outcomes (6)

• AUC0-tlast of Midazolam

  Area under the plasma concentration-time curve from 0 to the time of the last observed concentration (h\*pg/mL) on day 1 and day 14. The timepoints at which the data were collected to create the curve are as follows: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours postdose.

  Day 1 and Day 14

• AUC0-inf of Midazolam

  Area under the plasma concentration-time curve from zero to infinite time on day 1 and day 14. The timepoints at which the data were collected to create the curve are as follows: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours postdose and extrapolation to infinity.

  Day 1 and Day 14

• Cmax of Midazolam

  maximum measured concentration of midazolam after administration of midazolam until the last collection time, i.e., 10 hours after dosing on day 1 and day 14

  Day 1 and Day 14

• AUC0-tlast of 1'-Hydroxymidazolam

  Area under the plasma concentration-time curve from 0 to the time of the last observed concentration (h\*pg/mL) on day 1 and day 14. The timepoints at which the data were collected to create the curve are as follows: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours postdose.

  Day 1 and Day 14

• AUC-inf of 1'-Hydroxymidazolam

  Area under the plasma concentration-time curve from 0 to the infinite time (h\*pg/mL) on day 1 and Day 14. The timepoints at which the data were collected to create the curve are as follows: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours postdose and extrapolation to infinity.

  Day 1 and Day 14

• Cmax of 1'-Hydroxymidazolam

  maximum measured concentration of 1'-Hydroxymidazolam after administration of midazolam until the last collection time, i.e., 10 hours after dosing

  Day 1 and Day 14

Secondary Outcomes (9)

• Tmax of Midazolam

  Day 1 and Day 14

• CL/F of Midazolam

  Day 1 and Day 14

• Vz/F of Midazolam

  Day 1 and Day 14

• t1/2 of Midazolam

  Day 1 and Day 14

• Tmax of 1'-Hydroxymidazolam

  Day 1 and Day 14

Study Arms (1)

Midazolam/Vamorolone

EXPERIMENTAL

Single oral dose midazolam 2.5mg on day 1 Single oral suspension vamorolone 6mg/kg on day 3 to day 13 Single oral dose midazolam 2.5mg + Single oral suspension vamorolone 6mg/kg on day 14

Drug: Vamorolone; Drug: Midazolam

Interventions

Vamorolone DRUG

Days 3 to 14: 6 mg/kg vamorolone once daily.

Also known as: Test Drug

Midazolam/Vamorolone

Midazolam DRUG

Day 1 and 14: Single oral doses of 2.5 mg midazolam

Also known as: Reference Drug

Midazolam/Vamorolone

Eligibility Criteria

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

You may qualify if:

• Age of 18 to 55 years inclusive, at the time of signing the informed consent.
• Subject is overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, laboratory tests, and ECG.
• Body weight ≥ 50 kg and a BMI ≥ 18 kg/m2 and ≤ 29.9 kg/m2 at screening.
• Male and female. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Male subjects:
• If the subject is a sexually active man and not surgically sterilized, he must be willing to:
• Abstain from sexual intercourse or
• Use a condom plus another form of contraception, (e.g., spermicide, IUD, birth control pills taken by female partner) if engaging in sexual intercourse with a woman who could become pregnant.
• Use a condom during sexual intercourse with pregnant or lactating women.
• Must not father a child and must refrain from donating sperm from administration of the first dose and up to 3 months after the last dose of study treatment.
• Female subjects:
• All women (regardless of their status, i.e. WOCBP and WONCBP; for definitions see Section 10.4.1) must have a negative serum β-hCG pregnancy test prior to the initiation of the study treatments. FSH levels of suspected postmenopausal females must be \> 30 mIU/mL.
• Vamorolone has the potential to induce CYP3A4, which may result in a reduction in the effectiveness of contraceptives that are metabolized by CYP3A4 such as hormonal contraceptives when co-administered with vamorolone. Therefore, hormonal contraceptives by any route of administration are contraindicated.
• Women participating in the study must be either:
• WONCBP or

You may not qualify if:

• A past medical history of clinically significant abnormalities or a history/family history of long QT interval syndrome, structural cardiac abnormalities (including but not limited to hypertrophic cardiomyopathy, valvulopathy, and congenital defects), or cardiogenic syncope.
• An abnormal ECG, defined as:
• PR \> 215 msec and \< 100 msec, QRS complex \> 120 msec; QTcF \> 450 msec by automated reading
• Any clinically significant ST/T wave abnormalities
• Any atrial or ventricular arrhythmias
• A past medical history of myocardial infarction, angina pectoris, atherosclerosis or other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension).
• A past medical history of peptic ulcers, diverticulitis, and non-specific ulcerative colitis.
• History of complaints of frequent dizziness and /or vomiting spells or lightheadedness ("frequent" defined as incidence occurs more than once every week) or history of/or present sleep apnea.
• Any history or evidence of any clinically relevant, gastrointestinal, respiratory, hepatic, renal, endocrinologic, hematologic, immunologic, metabolic, genitourinary, pulmonary, neurologic, dermatologic, musculoskeletal, and/or other major disease or malignancy as determined by medical evaluation (including physical examination) capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatments; or interfering with the interpretation of data.
• Known Gilbert's syndrome.
• Any clinically relevant history of allergic conditions requiring hospitalization or prolonged systemic treatment (including drug allergies, allergic asthma, eczema, allergies requiring therapy with corticosteroids or anaphylactic reactions); but excluding untreated, asymptomatic, seasonal allergies at time of dosing or allergic contact sensitizations (e.g., nickel allergy).
• Known or suspected hypersensitivity or contraindications to vamorolone and/or midazolam or any components of the formulation used.
• Relevant current acute or chronic/recurrent viral, bacterial, fungal, or parasitic infections (e.g., pulmonary/upper respiratory, gastrointestinal, urinary, skin, or ENT infections) at screening or within 28 days prior to administration of the study treatments.
• Use of any concomitant medication or any drugs / medicines (including dietary supplements, natural and herbal remedies, and hormone replacement therapy) within 2 weeks or 5 times the half-life of the respective drug, whichever is longer, prior to the first administration of the study treatments.
• Occasional use of paracetamol up to 2 g/day or ibuprofen up to 1.2 g/day (medicinal products in their original packaging, approved and marketed in Germany) is permitted.

Sponsors & Collaborators

• Santhera Pharmaceuticals: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

MeSH Terms

Interventions

VBP15 compound; Drug Evaluation; Midazolam

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Shabir Hasham MD, Chief Medical Officer
• Organization: Santhera Pharmaceuticals LTD

shabir.hasham@santhera.com

+41 79 520 95 18

Study Officials

• Michael Lissy, MD

  Nuvisan GmbH

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Model Details: A single-center, open-label, single-arm, fixed-sequence, design. Healthy male and female subjects (18 to 55 years, inclusive) are eligible.

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: November 14, 2024
• Study Start: August 13, 2024
• Primary Completion: September 24, 2024
• Study Completion: October 16, 2024
• Last Updated: December 15, 2025
• Results First Posted: December 15, 2025

Record last verified: 2025-12

Locations

DE (1)