Evaluation of Vamorolone Mineralocorticoid Receptor Antagonism in Healthy Subjects

NCT06649409 | Completed Phase 1 Results

• 3 other identifiers: SNT-I-VAM-0262024-512101-60-00N-A-PH1-23-067
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate if the trial drug vamorolone is able to block a specific receptor in the body called mineralocorticoid receptor. This receptor helps to regulate salt and water balance.

Conditions

Pharmacodynamic

Keywords

Mineralocorticoid Receptor Antagonism

Outcome Measures

Primary Outcomes (1)

• Determination of the Ratio of Sodium to Potassium (Na/K) in Urine

  Amounts of Na and K were calculated by multiplying the respective concentration by the volume of urine for each collection interval. The considered timepoints were: Day 1: 24-9 h and 9-0 h predose of vamorolone/eplerenone; Day 2: 0-2 h, 2-4 h, 4-6 h, 6-8 h, 8-10 h, 10-12 h, 12-14 h, 14-16 h, 16-24 h postdose vamorolone/eplerenone or corresponding timepoint for negative control arm with fludrocortisone administrations (no treatment) Day 3: 24-32 h, 32-40 h, 40-48 h postdose vamorolone/eplerenone or corresponding timepoint for negative control arm with fludrocortisone administrations (no treatment) The individual Na/K ratio was then calculated for each urine collection interval using the amounts of Na and K. The corresponding logarithm of the Na/K ratio was determined. To avoid negative values, the ratio was multiplied by 10 before transformation, i.e., log10(10\*Na/K).

  Day 1, Day 2 and Day 3

Secondary Outcomes (10)

• Vamorolone PK Parameter AUC0-tlast

  Day 2

• Vamorolone PK Parameter AUC0-inf

  Day 2

• Vamorolone PK Parameter Cmax

  Day 2

• Vamorolone PK Parameter Tmax

  Day 2

• Vamorolone PK Parameter t1/2

  Day 2

Study Arms (3)

Study arm 1 vamorolone

EXPERIMENTAL

Vamorolone 20 mg/kg single dose on Day 2 and Fludrocortisone challenge on Days 1 to 3

Drug: Vamorolone; Drug: Fludrocortisone

Study arm 2 (positive control arm): eplerenone

ACTIVE COMPARATOR

Eplerenone 200 mg single dose on Day 2 and Fludrocortisone challenge on Days 1 to 3

Drug: Eplerenone; Drug: Fludrocortisone

Study arm 3 (negative control arm): no "active" treatment

OTHER

Fludrocortisone challenge on Days 1 to 3

Drug: Fludrocortisone

Interventions

Vamorolone DRUG

vamorolone 20 mg/kg single dose on Day 2

Also known as: experimental drug

Study arm 1 vamorolone

Eplerenone DRUG

Eplerenone 200 mg single dose on Day 2

Also known as: positive control

Study arm 2 (positive control arm): eplerenone

Fludrocortisone DRUG

Fludrocortisone challenge on Days 1 to 3 (for all subjects): Day 1: -Fludrocortisone 1 mg at 9 h predose vamorolone /eplerenone administration/corresponding timepoint for negative control arm Day 2: * Fludrocortisone 0.5 mg at the same time of vamorolone/eplerenone administration in the morning (0 h) /corresponding timepoint for negative control arm. * Fludrocortisone 0.1 mg at 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 14 h vamorolone/eplerenone postdose administration/corresponding timepoint for negative control arm. * Fludrocortisone 0.5 mg at 16 h vamorolone/eplerenone postdose administration/corresponding timepoint for negative control arm. Day 3: -Fludrocortisone 0.1 mg at 24 h vamorolone/eplerenone postdose administration on Day 2/corresponding timepoint for negative control arm.

Also known as: auxiliary medicinal product - mineralocorticoid agonist

Study arm 1 vamorolone; Study arm 2 (positive control arm): eplerenone; Study arm 3 (negative control arm): no "active" treatment

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• 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.
• Male 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
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• 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, Intrauterine device (IUD), birth control pills taken by female partner, diaphragm with spermicide) 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.
• Subject is a non-smoker for at least 3 months prior to exposure to the study treatments.
• Subjects must also have abstained from use of other nicotine containing products (e.g., nicotine patch, chewing gum or e-cigarettes) for at least 3 months before exposure to the study treatment.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the Informed consent form (ICF) and in this protocol prior to any clinical study specific procedure.
• Supine systolic blood pressure of ≥ 90 mmHg and ≤ 140 mmHg, diastolic blood pressure of ≥ 50 mmHg and ≤ 90 mmHg, pulse rate of ≥ 45 bpm and ≤ 90 bpm, and tympanic body temperature of ≥ 35.0 and ≤ 37.5°C at screening.
• Subjects must be able to communicate well with the Investigator and comply with the protocol requirements, instructions, and protocol related restrictions (e.g., dietary, fluid and lifestyle restrictions from screening to study completion)
• Subjects must be able to swallow the study treatments as per protocol

You may not qualify if:

• A past medical history of clinically significant abnormalities or a history/family history of long QT interval syndrome.
• An abnormal ECG, defined as:
• Pulse rate (PR) \> 215 msec and \< 120 msec, QRS (Part of electrocardiographic wave representing ventricular depolarization) complex \> 120 msec; QTcF \> 440 msec by automated reading
• Any clinically significant cardiac conduction 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.
• 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 the study treatments or any components of the formulation used, e.g., vamorolone, eplerenone and fludrocortisone.
• Relevant current acute or chronic/recurrent viral, bacterial, fungal or parasitic infections (e.g., pulmonary/upper respiratory, gastrointestinal, urinary, skin, or ear, nose and throat (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 (medicinal product in its original packaging, approved and marketed in Germany) is permitted.

Sponsors & Collaborators

• Santhera Pharmaceuticals: lead

Study Sites (1)

Nuvisan GmbH

Neu-Ulm, 89231, Germany

Location

Related Publications (1)

• de Vera A, Clemens PR, Dang UJ, Dutreix C, Gresko E, Guglieri M, Hagerty L, Hasham S, Damsker J, Hathout Y, Linden A, Berglund A, Tobin R, Wahbi K, Hoffman EP. Mineralocorticoid receptor antagonism of vamorolone: Evidence from LIONHEART and VISION-DMD clinical trials. Steroids. 2025 Nov;223:109689. doi: 10.1016/j.steroids.2025.109689. Epub 2025 Sep 14.

  PMID: 40957504 DERIVED

MeSH Terms

Interventions

VBP15 compound; Drugs, Investigational; Eplerenone; Fludrocortisone

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydrocortisone; Pregnenediones

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

• Steffen Haffner, MD

  Nuvisan GmbH

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Model Details: This study will be conducted in a single-center, randomized, open-label, 3-arm, parallel-group, positive- and negative-controlled design.

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: October 18, 2024
• Study Start: June 5, 2024
• Primary Completion: June 29, 2024
• Study Completion: July 6, 2024
• Last Updated: September 11, 2025
• Results First Posted: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)