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

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ClinicalTrials.gov Identifier: NCT02882217
Recruitment Status : Completed
First Posted : August 29, 2016
Last Update Posted : May 18, 2017
Sponsor:
Information provided by (Responsible Party):
EURRUS Biotech GmbH

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: XC8 (histamine glutarimide) Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
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 Start Date : August 2016
Actual Primary Completion Date : May 2017
Actual Study Completion Date : May 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Histamine

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



Primary Outcome Measures :
  1. Number of Adverse events per treatment arm [ Time Frame: Change from pre-dose up to Day 36 ]
    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

  2. Laboratory data [ Time Frame: Changes from Day 1 (pre-dose) till Day 2 ]
    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.

  3. Laboratory data [ Time Frame: Changes from Day 8 (pre-dose) till Day 10 ]
    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.

  4. Laboratory data [ Time Frame: Changes from Day 8 (pre-dose) till Day 15 ]
    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.

  5. Physical examination [ Time Frame: Day 1 ]
    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.

  6. Physical examination [ Time Frame: Day 8 ]
    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.

  7. 12-lead ECG [ Time Frame: Change from pre-dose till Day 2 ]
    12-lead ECG results will be analyzed descriptively

  8. 12-lead ECG [ Time Frame: Day 8 ]
    12-lead ECG results will be analyzed descriptively

  9. Vital signs [ Time Frame: Changes from pre-dose till Day 36 ]
    Vital signs (blood pressure, respiratory rate, pulse, and temperature) results will be analyzed descriptively.


Secondary Outcome Measures :
  1. Pharmacokinetics of XC8 by assessing AUCinf [ Time Frame: 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) ]
    Area under the plasma concentration-time curve extrapolated to infinity

  2. Pharmacokinetics of XC8 by assessing Cmax [ Time Frame: 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) ]
    Maximum plasma concentration

  3. Pharmacokinetics of XC8 by assessing AUC0-tlast [ Time Frame: 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) ]
    Area under the plasma concentration-time curve up to the last sampling time with a concentration above the limit of quantification

  4. Pharmacokinetics of XC8 by assessing AUC0-24 [ Time Frame: 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) ]
    Area under the plasma concentration-time curve up to 24 hours after study drug administration

  5. Pharmacokinetics of XC8 by assessing t1/2 [ Time Frame: 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) ]
    Terminal elimination half-life

  6. Pharmacokinetics of XC8 by assessing Tmax [ Time Frame: 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) ]
    Time to reach Cmax

  7. Pharmacokinetics of XC8 by assessing λz [ Time Frame: 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) ]
    Apparent first order terminal elimination rate constant

  8. Pharmacokinetics of XC8 by assessing Cav [ Time Frame: 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) ]
    Average concentration over one dosing interval

  9. Pharmacodynamic analyses: blood eosinophils [ Time Frame: changes from Day 1 (pre-dose) to Day 2 and Day 8 (pre-dose) to Day 22 ]
  10. Pharmacodynamic analyses: blood cytokines [ Time Frame: changes from Day 1 (pre-dose) to Day 2 and Day 8 (pre-dose) to Day 22 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02882217


Locations
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Austria
Karl Landsteiner Institut für experimentelle und klinische Pneumologie, Wolkersbergenstraße 1
Wien, Austria, 1130
Germany
Fraunhofer Institut für Toxikologie und Experimentelle Medizin ITEM, Feodor-Lynen-Str.15
Hannover, Germany, 30625
Sponsors and Collaborators
EURRUS Biotech GmbH
Investigators
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Study Director: Helmut Schmutz, Mag.iur. EURRUS Biotech GmbH

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Responsible Party: EURRUS Biotech GmbH
ClinicalTrials.gov Identifier: NCT02882217     History of Changes
Other Study ID Numbers: PULM-XC8-03
First Posted: August 29, 2016    Key Record Dates
Last Update Posted: May 18, 2017
Last Verified: May 2017
Keywords provided by EURRUS Biotech GmbH:
Double-blind
Randomized
Dose-escalating
Placebo-controlled
Phase I
Healthy volunteers
Bronchial asthma
Histamine glutarimide
EURRUS
Additional relevant MeSH terms:
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Histamine
Histamine phosphate
Histamine Agonists
Histamine Agents
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Glutarimide
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protein Synthesis Inhibitors
Enzyme Inhibitors