Study to Assess Safety, Tolerability and Pharmacokinetics of XC221 in Healthy Volunteers

NCT03459391 | Completed Phase 1 DMC

• 1 other identifier: ARI-XC221-01
• Study Type: interventional
• Target: 32
• 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 drug XC221 after single and repeated oral administration in healthy volunteers. The volunteers received the study drug once, and then continued daily intake for 5 days after a 6-day break. The primary objective of the study was to evaluate the safety and tolerability profile for drug XC221 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 active pharmaceutical substance XC221GI and its metabolite XC221A.

Conditions

Influenza; Acute Respiratory Infection

Keywords

Healthy volunteers; Phase I; PHARMENTERPRISES

Outcome Measures

Primary Outcomes (1)

• Number of Adverse events per treatment arm

  Adverse events have been classified according to CTCAE ver 4.03. 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 28

Secondary Outcomes (10)

• Pharmacokinetics of XC221GI by assessing AUC0-inf

  Day 1 and 11 (Pre dose, 15 min, 30 min, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8,12 and 16 h post dose), Day 2 and Day 12 (24 h ±10 min post dose), Day 3 and Day 13 (48 h ±10 min post dose), Day 4 and Day 14 (72 h ±10 min post dose), Day 7 to 10 (Pre dose)

• Pharmacokinetics of XC221A by assessing AUC0-inf

  Day 1 and 11 (Pre dose, 15 min, 30 min, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8,12 and 16 h post dose), Day 2 and Day 12 (24 h ±10 min post dose), Day 3 and Day 13 (48 h ±10 min post dose), Day 4 and Day 14 (72 h ±10 min post dose), Day 7 to 10 (Pre dose)

• Pharmacokinetics of XC221GI by assessing Cmax

  Day 1 and 11 (Pre dose, 15 min, 30 min, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8,12 and 16 h post dose), Day 2 and Day 12 (24 h ±10 min post dose), Day 3 and Day 13 (48 h ±10 min post dose), Day 4 and Day 14 (72 h ±10 min post dose), Day 7 to 10 (Pre dose)

• Pharmacokinetics of XC221A by assessing Cmax

  Day 1 and 11 (Pre dose, 15 min, 30 min, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8,12 and 16 h post dose), Day 2 and Day 12 (24 h ±10 min post dose), Day 3 and Day 13 (48 h ±10 min post dose), Day 4 and Day 14 (72 h ±10 min post dose), Day 7 to 10 (Pre dose)

• Pharmacokinetics of XC221GI by assessing AUC0-t

  Day 1 and 11 (Pre dose, 15 min, 30 min, 1,1.5, 2, 2.5, 3, 4, 5, 6, 8,12 and 16 h post dose), Day 2 and Day 12 (24 h ±10 min post dose), Day 3 and Day 13 (48 h ±10 min post dose), Day 4 and Day 14 (72 h ±10 min post dose), Day 7 to 10 (Pre dose)

Study Arms (3)

XC221 60 mg

EXPERIMENTAL

Cohort 1:16 subjects were randomized in a 3:1 ratio to be treated either with 60 mg XC221 (12 subjects) or placebo (4 subjects, see placebo arm).

Drug: XC221 60 mg

XC221 200 mg

EXPERIMENTAL

Cohort 2: 16 subjects were randomized in a 3:1 ratio to be treated either with 200 mg XC221 (12 subjects) or placebo (4 subjects, see placebo arm).

Drug: XC221 200 mg

Placebo

PLACEBO COMPARATOR

Placebo comparator arm consists of 8 subjects (4 subjects from each cohort).

Drug: Placebo

Interventions

XC221 60 mg DRUG

The volunteers received the study drug once, and then continued daily intake for 5 days after a 6-day break.

XC221 60 mg

XC221 200 mg DRUG

The volunteers received the study drug once, and then continued daily intake for 5 days after a 6-day break.

XC221 200 mg

Placebo DRUG

The volunteers received the study drug once, and then continued daily intake for 5 days after a 6-day break.

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Non-smoking men aged 18 to 45 years (inclusive);
• Verified diagnosis "healthy" according to standard clinical, laboratory and instrumental methods of examination;
• Body mass \>50 kg and body mass index of 18.5 to 30 kg/m2 (inclusive);
• Negative result of tests for alcohol and drugs;
• 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:

• Chronic diseases of cardiovascular, bronchopulmonary, neuroendocrine, musculoskeletal system and also disease of digestive tract, liver, kidneys, blood;
• Laboratory abnormalities at screening;
• Surgical interventions on digestive tract in the anamnesis (except for an appendectomies);
• Systolic pressure is less than 90 mm Hg. or more than 130 mm Hg., diastolic pressure is less than 60 mm Hg. or more than 85 mm Hg., pulse rate less than 60/min. or more than 80/min.;
• 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; smoking 3 months before screening;
• History of allergies (including medicines and food products);
• 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;
• Acute infectious diseases less than 4 weeks before the start of the study;
• Impossibility to understand or follow protocol instructions/

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

Influenza, Human

Interventions

XC221

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract 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 XC221 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. 2 doses of XC221/placebo (60 mg and 200 mg) were used in the study.The duration of exposure to the study drug was 6 days in each cohort: Day 1, once, at the step of single administration, and then in 6 days, daily, 1 time a day for 5 days at the step of multiple administration.

Study Record Dates

• First Submitted: February 26, 2018
• First Posted: March 8, 2018
• Study Start: May 22, 2017
• Primary Completion: September 26, 2017
• Study Completion: September 26, 2017
• Last Updated: March 8, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)