Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers
Primary Purpose
Acute Nasopharyngitis
Status
Completed
Phase
Phase 1
Locations
Austria
Study Type
Interventional
Intervention
2-Deoxyglucose
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Acute Nasopharyngitis focused on measuring Virus disease, Respiratory infection, Common cold virus, Rhinovirus
Eligibility Criteria
Inclusion Criteria:
- Healthy male or female volunteers, age ≥ 18 years old at screening
- Females must be post-menopausal (> 1 year since last menstruation)
- Able to comprehend and to give informed consent
- Able to cooperate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures
- Undergone full immunisation against SARS-CoV2 or status post infection with SARS-CoV2 (both as defined by the Austrian Ministry of Health)
Exclusion Criteria:
- Frequent epistaxis (equal to or greater than 1/month)
- Hypo- or anosmia
- Symptoms of rhinitis, allergy or common cold disease at screening and at study initiation
- Medical history of diabetes mellitus of any type
- Clinically relevant abnormal findings at screening
- Preceding nasal surgery or sinus surgery
- Medical history of allergic rhinitis or chronic condition of the upper or lower respiratory tract with active symptoms within 30 days prior to screening
- SARS-CoV-2 infection positive by PCR test at screening
- Vulnerable subjects as defined by GCP
- Subjects in a dependency relationship towards the investigators, e.g. as employees
- Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the investigator for the subject to be able to comply fully with study procedures
- Use of medication (including prophylactic treatments) during 2 weeks before the start of the study, which in the judgment of the investigator may adversely affect the subject's welfare or the integrity of the study's results
- Concurrent treatment with other experimental product or participation in another clinical trial with any investigational product within 30 days or 5 elimination half-lives (whichever is longer) prior to treatment start
- Scheduled vaccination appointments during the study period
Sites / Locations
- Medical University of Vienna
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Study drug
Placebo
Arm Description
Each subject receives either a single dose (SAD) or a multiple dose (MAD) of a 3.5% 2-Deoxyglucose as nasal spray solution. The starting dose for the first cohort is 3.5 mg/day up to a maximum of 84 mg/day at cohort 6.
Each subject receives either a single (SAD) or multiple (MAD) dose of placebo. The dose for each cohort is corresponding the amount of solution needed in the verum group.
Outcomes
Primary Outcome Measures
Adverse drug reactions (ADRs)
Number of ADRs after a single dose of 2-DG assessed by type, frequency and severity of ADRs graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Adverse drug reactions (ADRs)
Number of ADRs after multiple doses of 2-DG assessed by type, frequency and severity of ADRs graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Secondary Outcome Measures
Biodistribution of a single dose of 2-DG
Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
Biodistribution of multiple doses of 2-DG
Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
Local tolerability of a single dose of 2-DG
Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).
Local tolerability of multiple doses of 2-DG
Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).
Olfactory function after a single dose of 2-DG
Change in olfactory capacity using sniffing sticks measured by Threshold-Discrimination-Identification score (TDI score). Minimum value = 0 , maximum value= 48. A higher score means a better outcome.
Olfactory function after multiple doses of 2-DG
Change in olfactory capacity using sniffing sticks measured by Threshold-Discrimination-Identification score (TDI score). Minimum value = 0 , maximum value= 48. A higher score means a better outcome.
Premature terminations due to ADRs after a single dose of 2-DG
Number of premature terminations due to ADRs that are assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Premature terminations due to ADRs after multiple doses of 2-DG
Number of premature terminations due to ADRs that are assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Adverse events after single dose 2-DG
Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Adverse events after multiple doses 2-DG
Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Full Information
NCT ID
NCT05314933
First Posted
February 3, 2022
Last Updated
October 11, 2023
Sponsor
G.ST Antivirals GmbH
1. Study Identification
Unique Protocol Identification Number
NCT05314933
Brief Title
Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers
Official Title
A Single/Multiple Ascending Dose Phase 1 Study Of The Safety, Tolerability, And Pharmacokinetics Of Intranasal 2-Deoxy-D-Glucose In Normal Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
March 3, 2022 (Actual)
Primary Completion Date
August 1, 2023 (Actual)
Study Completion Date
September 27, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
G.ST Antivirals GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
2-DG-01 is a randomized, double-blind, placebo-controlled, single and multiple ascending dose phase 1 study assessing safety, tolerability and pharmacokinetics of 2-DG in normal healthy volunteers (NHV). The safety and pharmacokinetics of 2-DG are assessed after single or multiple intranasal administrations.
Detailed Description
2-DG-01 is a randomized, placebo-controlled, double- blind single and multiple ascending dose phase 1 study in normal healthy male and female volunteers aged 18 years or older.
The primary objective of this study is to assess the clinical safety and tolerability of intranasal 2-DG in NHVs.
The secondary objective of this study is to assess the human pharmacokinetics of 2-DG.
The study is divided in two sub-parts: Part A, a single ascending dose (SAD) study of 2-DG and Part B, a multiple ascending dose (MAD) study.
Part A consists of 3 cohorts: Cohorts 1 and 2 with a randomization ratio for 2-DG to placebo of 4:1 and Cohort 3 with a randomization ratio for 2-DG to placebo of 8:2.
Part B consists of 3 cohorts: Cohort 4 with a a randomization ratio for 2-DG to placebo of 4:1 and Cohorts 5 and 6 with a randomization ratio for 2-DG to placebo of 8:2.
Cohorts 1, 2 and 4 will also be controlled by randomized intranasal application of placebo into the opposite nostril to obtain an intra-individual estimate for local tolerability. Other cohorts will receive either 2-DG or placebo into both nostrils.
Interim safety reviews are performed by a Data Monitoring Committee.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Nasopharyngitis
Keywords
Virus disease, Respiratory infection, Common cold virus, Rhinovirus
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Study drug
Arm Type
Active Comparator
Arm Description
Each subject receives either a single dose (SAD) or a multiple dose (MAD) of a 3.5% 2-Deoxyglucose as nasal spray solution.
The starting dose for the first cohort is 3.5 mg/day up to a maximum of 84 mg/day at cohort 6.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Each subject receives either a single (SAD) or multiple (MAD) dose of placebo. The dose for each cohort is corresponding the amount of solution needed in the verum group.
Intervention Type
Drug
Intervention Name(s)
2-Deoxyglucose
Other Intervention Name(s)
2-DG, 2-Deoxy-D-glucose
Intervention Description
Intranasal administration
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Intranasal administration
Primary Outcome Measure Information:
Title
Adverse drug reactions (ADRs)
Description
Number of ADRs after a single dose of 2-DG assessed by type, frequency and severity of ADRs graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
until 24 hours after single drug dosing
Title
Adverse drug reactions (ADRs)
Description
Number of ADRs after multiple doses of 2-DG assessed by type, frequency and severity of ADRs graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
until 168 hours after start of multiple drug dosing
Secondary Outcome Measure Information:
Title
Biodistribution of a single dose of 2-DG
Description
Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
Time Frame
baseline,0.5 hours, 2 hours, 4 hours, 6 hours after single drug dosing
Title
Biodistribution of multiple doses of 2-DG
Description
Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
Time Frame
baseline, 12 hours, 15 hours, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
Title
Local tolerability of a single dose of 2-DG
Description
Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).
Time Frame
baseline, 6 hours, 24 hours after single drug dosing
Title
Local tolerability of multiple doses of 2-DG
Description
Abnormal physical examination findings in the nasal cavity (type, frequency, severity of medical abnormalities, scoring of self-reported symptoms).
Time Frame
baseline, 3 hours, 12 hours, 24 hours after start of multiple drug dosing
Title
Olfactory function after a single dose of 2-DG
Description
Change in olfactory capacity using sniffing sticks measured by Threshold-Discrimination-Identification score (TDI score). Minimum value = 0 , maximum value= 48. A higher score means a better outcome.
Time Frame
baseline, 24 hours after single drug dosing
Title
Olfactory function after multiple doses of 2-DG
Description
Change in olfactory capacity using sniffing sticks measured by Threshold-Discrimination-Identification score (TDI score). Minimum value = 0 , maximum value= 48. A higher score means a better outcome.
Time Frame
baseline, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
Title
Premature terminations due to ADRs after a single dose of 2-DG
Description
Number of premature terminations due to ADRs that are assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
until 24 hours after single drug dosing
Title
Premature terminations due to ADRs after multiple doses of 2-DG
Description
Number of premature terminations due to ADRs that are assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
until 168 hours after start of multiple drug dosing
Title
Adverse events after single dose 2-DG
Description
Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
until 24 hours after single drug dosing
Title
Adverse events after multiple doses 2-DG
Description
Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Time Frame
until 168 hours after start of multiple drug dosing
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy male or female volunteers, age ≥ 18 years old at screening
Females must be post-menopausal (> 1 year since last menstruation)
Able to comprehend and to give informed consent
Able to cooperate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures
Undergone full immunisation against SARS-CoV2 or status post infection with SARS-CoV2 (both as defined by the Austrian Ministry of Health)
Exclusion Criteria:
Frequent epistaxis (equal to or greater than 1/month)
Hypo- or anosmia
Symptoms of rhinitis, allergy or common cold disease at screening and at study initiation
Medical history of diabetes mellitus of any type
Clinically relevant abnormal findings at screening
Preceding nasal surgery or sinus surgery
Medical history of allergic rhinitis or chronic condition of the upper or lower respiratory tract with active symptoms within 30 days prior to screening
SARS-CoV-2 infection positive by PCR test at screening
Vulnerable subjects as defined by GCP
Subjects in a dependency relationship towards the investigators, e.g. as employees
Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the investigator for the subject to be able to comply fully with study procedures
Use of medication (including prophylactic treatments) during 2 weeks before the start of the study, which in the judgment of the investigator may adversely affect the subject's welfare or the integrity of the study's results
Concurrent treatment with other experimental product or participation in another clinical trial with any investigational product within 30 days or 5 elimination half-lives (whichever is longer) prior to treatment start
Scheduled vaccination appointments during the study period
Facility Information:
Facility Name
Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers
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