XC8 Safety, Tolerability and Pharmacokinetics in Healthy Volunteers

NCT03441815 | Completed Phase 1 DMC

• 1 other identifier: PULM-XC8-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

A double-blind, randomized, placebo-controlled, Phase I clinical study of the safety and tolerability of increasing doses of XC8 after single and repeated oral administration in healthy volunteers. The volunteers received the study drug once, and then continued daily intake for 14 days after a 6-day break. The primary objective of the study was to evaluate the safety and tolerability profile for XC8 after single and multiple administration based on the frequency and severity of adverse events and changes in vital signs, laboratory results, electrocardiography and results of the physical examination. The secondary objective of the study was to assess pharmacokinetics of XC8.

Conditions

Asthma

Keywords

Healthy volunteers; Phase I; Histamine glutarimide; PHARMENTERPRISES

Outcome Measures

Primary Outcomes (3)

• 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 to Day 50

• 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 till Day 36

• 12-lead ECG

  12-lead ECG results will be analyzed descriptively

  Change from pre-dose till Day 36

Secondary Outcomes (7)

• Pharmacokinetics of XC8 by assessing AUC0-inf

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4, 6 and 10 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose), Day 3 (48 hours ±10 minutes post dose), Day 4 (72 hours ±10 minutes post dose), Day 8 to 12 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing Cmax

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4, 6 and 10 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose), Day 3 (48 hours ±10 minutes post dose), Day 4 (72 hours ±10 minutes post dose), Day 8 to 12 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing AUC0-t

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4, 6 and 10 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose), Day 3 (48 hours ±10 minutes post dose), Day 4 (72 hours ±10 minutes post dose), Day 8 to 12 and 15 (Pre dose)

• Pharmacokinetics of XC8 by assessing Tmax

  Day 1 and 21 (Pre dose, and 20 min, 40 min, 1, 2, 4, 6 and 10 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose), Day 3 (48 hours ±10 minutes post dose), Day 4 (72 hours ±10 minutes post dose), Day 8 to 12 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, 6 and 10 hours post dose), Day 2 and Day 22 (24 hours ±10 minutes post dose), Day 3 (48 hours ±10 minutes post dose), Day 4 (72 hours ±10 minutes post dose), Day 8 to 12 and 15 (Pre dose)

Study Arms (5)

XC8 2 mg

EXPERIMENTAL

Cohort 1: 6 subjects were randomized in a 2:1 ratio to be treated either with 2 mg XC8 (4 subjects) or placebo (2 subjects, see placebo arm).

Drug: XC8

XC8 10 mg

EXPERIMENTAL

Cohort 2: 6 subjects were randomized in a 2:1 ratio to be treated either with 10 mg XC8 (4 subjects) or placebo (2 subjects, see placebo arm).

Drug: XC8

XC8 50 mg

EXPERIMENTAL

Cohort 3: 6 subjects were randomized in a 2:1 ratio to be treated either with 50 mg XC8 (4 subjects) or placebo (2 subjects, see placebo arm).

Drug: XC8

XC8 200 mg

EXPERIMENTAL

Cohort 4: 10 subjects were randomized in a 4:1 ratio to be treated either with 200 mg XC8 (8 subjects) or placebo (2 subjects, see placebo arm).

Drug: XC8

Placebo

PLACEBO COMPARATOR

Placebo comparator arm consists of 8 subjects (2 subjects in each cohort).

Drug: Placebo

Interventions

XC8 DRUG

Also known as: Histamine glutarimide

XC8 10 mg; XC8 2 mg; XC8 200 mg; XC8 50 mg

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• Non-smoking men aged 18 to 50 years (inclusive);
• Verified diagnosis "healthy" according to standard clinical, laboratory and instrumental methods of examination;
• Body mass index of 19 to 30 kg/m2 (inclusive);
• Consent to use reliable methods of contraception during the study and 3 months after its completion (condoms with spermicide);
• Signed patient information sheet and informed consent form for participation in the study.

You may not qualify if:

• Hepatic disorder or renal disease; any other disease that, in the opinion investigator, may affect the results of the study, or may lead to the health aggravation during the study;
• Laboratory abnormalities at screening;
• Course intake of medicinal products (including herbs and biologically active additives) for preventive or curative purposes within 1 month prior to screening;
• Antibodies to HIV and hepatitis C virus, the presence of the hepatitis B surface antigen, a positive syphilis test;
• The presence of a sleep disorder (for example, night work, sleep disturbances, insomnia, recent return from another time zone, etc.);
• Signs of alcohol or drug abuse; taking alcohol or drugs during 4 days before screening;
• History of allergies (including medicines and food products);
• Symptomatic rhinitis in anamnesis during 2 years prior to screening (allergic rhinitis, non-allergic rhinitis or pollinosis);
• Blood donation / plasma, surgical intervention (in a hospital environment) during 12 weeks before screening;
• Participation in other clinical trials or taking the study drug during 3 months before screening;
• Impossibility to understand or follow protocol instructions;
• Smoking 3 months before screening;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;
• Acute infectious diseases less than 4 weeks before the start of the study.

Sponsors & Collaborators

• PHARMENTERPRISES LLC: lead

Study Sites (1)

SBEI HPE The First Moscow State Medical University n.a. Sechenov of Ministry of Health of Russian Federation, University Hospital #2, Department of Development of New Medicines

Moscow, 119435, Russia

Location

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Blinding was carried out by using Placebo equivalent to XC8 tablets without active substance and the corresponding labeling of the study drug.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The dose cohorts were included into the study subsequently based on preliminary safety results evaluation performed by the Data Safety Monitoring Committee. 4 doses of XC8/placebo (2 mg, 10 mg, 50 mg and 200 mg) were used in the study.The duration of exposure to the study drug was 15 days in each cohort: Day 1, once, at the step of single administration, and then in 6 days, daily, 1 time a day for 14 days at the step of multiple administration.

Study Record Dates

• First Submitted: January 11, 2018
• First Posted: February 22, 2018
• Study Start: February 14, 2015
• Primary Completion: July 7, 2015
• Study Completion: July 7, 2015
• Last Updated: February 22, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)