Study to Assess Pharmacokinetics, Safety, and Tolerability of XC-8

NCT02882217 | Completed Phase 1

• 1 other identifier: PULM-XC8-03
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 2

Brief Summary

The study focusses on the evaluation of safety and tolerability of the XC8. The design of the study involves sequential dosing of cohorts (group of volunteers), taking increasing doses of the product after receiving conclusion and recommendation for further continuation of the study from the Dose Escalation Committee.

Conditions

Asthma

Keywords

Double-blind; Randomized; Dose-escalating; Placebo-controlled; Phase I; Healthy volunteers; Bronchial asthma; Histamine glutarimide; EURRUS

Outcome Measures

Primary Outcomes (9)

• Number of Adverse events per treatment arm

  Adverse events will be summarized descriptively by treatment arm. Verbatim terms will be mapped to preferred terms and organ systems using the current Medical Dictionary for Regulatory Activities version. For each preferred term, frequency counts and percentages will be calculated by cohort.The nature, severity, seriousness, and relationship to study medication will be summarized for all study subjects

  Change from pre-dose up to Day 36

• Laboratory data

  Laboratory data (hematology, biochemistry and urinalysis) will be summarized by treatment arm. Changes from pre-dose will be presented using shift tables (employing the categories 'normal', 'abnormal, clinically not significant' and 'abnormal, clinically significant') and absolute changes in laboratory values, if appropriate.

  Changes from Day 1 (pre-dose) till Day 2

• Laboratory data

  Laboratory data (hematology, biochemistry and urinalysis) will be summarized by treatment arm. Changes from pre-dose will be presented using shift tables (employing the categories 'normal', 'abnormal, clinically not significant' and 'abnormal, clinically significant') and absolute changes in laboratory values, if appropriate.

  Changes from Day 8 (pre-dose) till Day 10

• Laboratory data

  Laboratory data (hematology, biochemistry and urinalysis) will be summarized by treatment arm. Changes from pre-dose will be presented using shift tables (employing the categories 'normal', 'abnormal, clinically not significant' and 'abnormal, clinically significant') and absolute changes in laboratory values, if appropriate.

  Changes from Day 8 (pre-dose) till Day 15

• Physical examination

  Physical examination results will be listed for following: general appearance, skin, head, eyes, ears, nose, throat, neck (including thyroid), lymph nodes, chest, heart, abdomen (including liver examination), extremities, and nervous system.

  Day 1

• Physical examination

  Physical examination results will be listed for following: general appearance, skin, head, eyes, ears, nose, throat, neck (including thyroid), lymph nodes, chest, heart, abdomen (including liver examination), extremities, and nervous system.

  Day 8

• 12-lead ECG

  12-lead ECG results will be analyzed descriptively

  Change from pre-dose till Day 2

• 12-lead ECG

  12-lead ECG results will be analyzed descriptively

  Day 8

• Vital signs

  Vital signs (blood pressure, respiratory rate, pulse, and temperature) results will be analyzed descriptively.

  Changes from pre-dose till Day 36

Secondary Outcomes (10)

• Pharmacokinetics of XC8 by assessing AUCinf

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4 and 8 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose); Day 8 to 11, 13 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing Cmax

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4 and 8 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose); Day 8 to 11, 13 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing AUC0-tlast

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4 and 8 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose); Day 8 to 11, 13 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing AUC0-24

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4 and 8 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose); Day 8 to 11, 13 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing t1/2

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4 and 8 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose); Day 8 to 11, 13 and 15 (Pre dose)

Study Arms (4)

XC8 10mg

ACTIVE COMPARATOR

Cohort 1: 8 subjects will be randomized in a 3:1 ratio to be treated either with 10mg XC8 (6 subjects) or placebo (2 subjects, see placebo arm)

Drug: XC8 (histamine glutarimide)

XC8 50mg

ACTIVE COMPARATOR

Cohort 2: 8 subjects will be randomized in a 3:1 ratio to be treated either with 50mg XC8 (6 subjects) or placebo (2 subjects, see placebo arm)

Drug: XC8 (histamine glutarimide)

XC8 200mg

ACTIVE COMPARATOR

Cohort 3: 16 subjects will be randomized in a 3:1 ratio to be treated either with 200mg XC8 (12 subjects) or placebo (4 subjects, see placebo arm)

Drug: XC8 (histamine glutarimide)

Placebo

PLACEBO COMPARATOR

Placebo comparator arm consists of 2 subjects in the cohorts 1 and 2 each and 4 subjects in the cohort 3.

Drug: Placebo

Interventions

XC8 (histamine glutarimide) DRUG

XC8 10mg; XC8 200mg; XC8 50mg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged 18 to 50 years;
• Generally good health;
• Body mass index of 19 to 30 kg/m² and \>50 kg body weight;
• Female subjects who are post-menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or practice a highly effective method of birth control, i.e. resulting in a failure rate of less than 1% per year when used consistently and correctly (e.g. implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence, or vasectomized partner). The birth control method must have been applied for at least 1 cycle before and until 3 months after administration of the study medication.
• Male subjects with a female partner of child-bearing potential agree to use a medically acceptable method of contraception (e.g. condoms, sexual abstinence, vasectomy) during the study, and until 3 months after the last intake of study medication.
• Subjects are willing and able (in the opinion of the investigator) to understand and comply with the procedures and evaluations of the study.
• Subjects must be willing and legally able to give written informed consent.

You may not qualify if:

• Hepatic or renal disease; any other disease, which may influence the clinical trial results or may lead to health worsening during the trial (according to the investigator's opinion);
• Clinically significant laboratory abnormalities;
• Use of any medication, including prophylaxis, within 1 month before screening (including herbal preparations and nutritional supplements);
• Positive test for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus HBV at Screening;
• Irregular sleep (e.g. night work, sleep disturbances, insomnia, returning from another time zone, etc.);
• History or current evidence of alcohol or drug abuse; alcohol or drug intake within 4 days before Screening;
• History or current evidence of allergic reactions (including reactions to medications and food);
• History or current evidence of symptomatic rhinitis within 2 years before Screening (allergic rhinitis, non-allergic rhinitis, or hay fever, excluding short-term viral infection - cold or influenza);
• Blood or plasma donation, or surgery (in hospital) within 12 weeks of Screening;
• Lactating or pregnant females; a positive pregnancy test before the first administration of investigational medicinal product or breastfeeding;
• Current or previous (within 3 months of enrollment) treatment with another investigational drug and/or medical device or participation in another clinical study;
• Previous enrollment in this clinical study;
• Inability to understand or follow protocol instructions;
• Smoking within 3 months before screening or throughout the study;
• Lactose intolerance;

Sponsors & Collaborators

• EURRUS Biotech GmbH: lead

Study Sites (2)

Karl Landsteiner Institut für experimentelle und klinische Pneumologie, Wolkersbergenstraße 1

Vienna, 1130, Austria

Location

Fraunhofer Institut für Toxikologie und Experimentelle Medizin ITEM, Feodor-Lynen-Str.15

Hanover, 30625, Germany

Location

Related Publications (1)

• Renner A, Romanova J, Ferko B, Schmutz H, Nebolsin V, Muller M, Badorrek P, Marth K, Pohl W. Safety, pharmacokinetics and pharmacodynamics of a novel anti-asthmatic drug, XC8, in healthy probands. Pulm Pharmacol Ther. 2019 Dec;59:101852. doi: 10.1016/j.pupt.2019.101852. Epub 2019 Oct 6.

  PMID: 31597083 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

histamine glutarimide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Helmut Schmutz, Mag.iur.

  EURRUS Biotech GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: August 29, 2016
• Study Start: August 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: May 18, 2017

Record last verified: 2017-05

Locations

DE (1); AU (1)