Clinical trial NCT02882217: Study to Assess Pharmacokinetics, Safety, and Tolerability of XC-8
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Double-blind
Randomized
Dose-escalating
Placebo-controlled
Phase I
Healthy volunteers
Bronchial asthma
Histamine glutarimide
EURRUS
Lead sponsor: EURRUS Biotech GmbH
Sponsor class: INDUSTRY
First posted: 2016-08-29
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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;

Primary outcomes:
measure: Number of Adverse events per treatment arm
timeFrame: Change from pre-dose up to Day 36
measure: Laboratory data
timeFrame: Changes from Day 1 (pre-dose) till Day 2
measure: Laboratory data
timeFrame: Changes from Day 8 (pre-dose) till Day 10
measure: Laboratory data
timeFrame: Changes from Day 8 (pre-dose) till Day 15
measure: Physical examination
timeFrame: Day 1
measure: Physical examination
timeFrame: Day 8
measure: 12-lead ECG
timeFrame: Change from pre-dose till Day 2
measure: 12-lead ECG
timeFrame: Day 8
measure: Vital signs
timeFrame: Changes from pre-dose till Day 36
Secondary outcomes:
measure: Pharmacokinetics of XC8 by assessing AUCinf
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing Cmax
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing AUC0-tlast
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing AUC0-24
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing t1/2
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing Tmax
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing λz
timeFrame: 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)
measure: Pharmacokinetics of XC8 by assessing Cav
timeFrame: 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)
measure: Pharmacodynamic analyses: blood eosinophils
timeFrame: changes from Day 1 (pre-dose) to Day 2 and Day 8 (pre-dose) to Day 22
measure: Pharmacodynamic analyses: blood cytokines
timeFrame: changes from Day 1 (pre-dose) to Day 2 and Day 8 (pre-dose) to Day 22
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Karl Landsteiner Institut für experimentelle und klinische Pneumologie, Wolkersbergenstraße 1
city: Hannover
country: Germany
facility: Fraunhofer Institut für Toxikologie und Experimentelle Medizin ITEM, Feodor-Lynen-Str.15
Study officials:
affiliation: EURRUS Biotech GmbH
name: Helmut Schmutz, Mag.iur.
role: STUDY_DIRECTOR
References:
citation: 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.