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

Double-blind, Randomized, Dose-escalating, Placebo-controlled Study to Assess Pharmacokinetics, Safety, and Tolerability of XC-8 After Single and Multiple Oral Doses in Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: XC8 (histamine glutarimide)

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1130
    • Karl Landsteiner Institut für experimentelle und klinische Pneumologie, Wolkersbergenstraße 1
• Germany
  • Hannover, Germany, 30625
    • Fraunhofer Institut für Toxikologie und Experimentelle Medizin ITEM, Feodor-Lynen-Str.15

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women aged 18 to 50 years;
2. Generally good health;
3. Body mass index of 19 to 30 kg/m² and >50 kg body weight;
4. 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.
5. 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.
6. Subjects are willing and able (in the opinion of the investigator) to understand and comply with the procedures and evaluations of the study.
7. Subjects must be willing and legally able to give written informed consent.

Exclusion Criteria:

1. 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);
2. Clinically significant laboratory abnormalities;
3. Use of any medication, including prophylaxis, within 1 month before screening (including herbal preparations and nutritional supplements);
4. Positive test for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus HBV at Screening;
5. Irregular sleep (e.g. night work, sleep disturbances, insomnia, returning from another time zone, etc.);
6. History or current evidence of alcohol or drug abuse; alcohol or drug intake within 4 days before Screening;
7. History or current evidence of allergic reactions (including reactions to medications and food);
8. 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);
9. Blood or plasma donation, or surgery (in hospital) within 12 weeks of Screening;
10. Lactating or pregnant females; a positive pregnancy test before the first administration of investigational medicinal product or breastfeeding;
11. Current or previous (within 3 months of enrollment) treatment with another investigational drug and/or medical device or participation in another clinical study;
12. Previous enrollment in this clinical study;
13. Inability to understand or follow protocol instructions;
14. Smoking within 3 months before screening or throughout the study;
15. Lactose intolerance;
16. History of allergic reactions to XC-8 or any inactive ingredients of the trial medication;
17. Employees of the sponsor or subjects who are employees or relatives of the investigator;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: XC8 10mg; 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)
Active Comparator: XC8 50mg; 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)
Active Comparator: XC8 200mg; 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 Comparator: Placebo; Placebo comparator arm consists of 2 subjects in the cohorts 1 and 2 each and 4 subjects in the cohort 3.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of XC8 by assessing AUCinf	Area under the plasma concentration-time curve extrapolated to infinity	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	Maximum plasma concentration	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	Area under the plasma concentration-time curve up to the last sampling time with a concentration above the limit of quantification	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	Area under the plasma concentration-time curve up to 24 hours after study drug administration	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	Terminal elimination half-life	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 Tmax	Time to reach 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 λz	Apparent first order terminal elimination rate constant	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 Cav	Average concentration over one dosing interval	Day 8 to 11, 13 and 15 (Pre dose); Day 21 (Pre dose, and 20 min, 40 min, 1, 2, 4 and 8 hours post dose), Day 22 (24 hours ±10 minutes post dose)
Pharmacodynamic analyses: blood eosinophils		changes from Day 1 (pre-dose) to Day 2 and Day 8 (pre-dose) to Day 22
Pharmacodynamic analyses: blood cytokines		changes from Day 1 (pre-dose) to Day 2 and Day 8 (pre-dose) to Day 22

Collaborators and Investigators

• Sponsor: EURRUS Biotech GmbH
• Investigators: Study Director: Helmut Schmutz, Mag.iur., EURRUS Biotech GmbH

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: August 1, 2016
• First Submitted That Met QC Criteria: August 26, 2016
• First Posted (Estimate): August 29, 2016

Study Record Updates

• Last Update Posted (Actual): May 18, 2017
• Last Update Submitted That Met QC Criteria: May 17, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Healthy volunteers; Placebo-controlled; Randomized; Double-blind; Phase I; Dose-escalating; Bronchial asthma; Histamine glutarimide; EURRUS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Synthesis Inhibitors; Histamine Agents; Histamine Agonists; Histamine; Glutarimide
• Other Study ID Numbers: PULM-XC8-03