Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers
Overview
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.
Full Title of Study: “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
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Prevention
- Masking: Triple (Participant, Investigator, Outcomes Assessor)
- Study Primary Completion Date: June 2023
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.
Interventions
- Drug: 2-Deoxyglucose
- Intranasal administration
- Other: Placebo
- Intranasal administration
Arms, Groups and Cohorts
- Active Comparator: Study drug
- 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.
- Placebo Comparator: Placebo
- 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.
Clinical Trial Outcome Measures
Primary Measures
- Adverse drug reactions (ADRs)
- Time Frame: until 24 hours after single drug dosing
- 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)
- Time Frame: until 168 hours after start of multiple drug dosing
- 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 Measures
- Biodistribution of a single dose of 2-DG
- Time Frame: baseline,0.5 hours, 2 hours, 4 hours, 6 hours after single drug dosing
- Analysis of 2-DG concentrations in plasma and nasal wash samples measured by LC-MS (µg/ml).
- Biodistribution of multiple doses of 2-DG
- Time Frame: baseline, 12 hours, 15 hours, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
- 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
- Time Frame: baseline, 6 hours, 24 hours after single drug dosing
- 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
- Time Frame: baseline, 3 hours, 12 hours, 24 hours after start of multiple drug dosing
- 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
- Time Frame: baseline, 24 hours after single drug dosing
- 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
- Time Frame: baseline, 24 hours, 72 hours, 168 hours after start of multiple drug dosing
- 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
- Time Frame: until 24 hours after single drug dosing
- 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
- Time Frame: until 168 hours after start of multiple drug dosing
- 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
- Time Frame: until 24 hours after single drug dosing
- 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
- Time Frame: until 168 hours after start of multiple drug dosing
- Number of AEs assessed by type, frequency and severity graded as per Common Terminology Criteria for Adverse Events (CTCAE).
Participating in This Clinical Trial
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
Gender Eligibility: All
Minimum Age: 18 Years
Maximum Age: 99 Years
Are Healthy Volunteers Accepted: Accepts Healthy Volunteers
Investigator Details
- Lead Sponsor
- G.ST Antivirals GmbH
- Provider of Information About this Clinical Study
- Sponsor
Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.