Safety and Pharmacokinetic Study of Intranasal 2-DG in Healthy Volunteers

A Single/Multiple Ascending Dose Phase 1 Study Of The Safety, Tolerability, And Pharmacokinetics Of Intranasal 2-Deoxy-D-Glucose In Normal Healthy Volunteers

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.

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.

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