A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of GP1681 in Healthy Adult Participants

Exclusion Criteria27

• A participant who meets any of the following criteria must be excluded from the study:
• Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period, until study completion.
• Prior or ongoing medical conditions, medical history, physical findings, or laboratory abnormality that, in the Investigator’s (or delegate’s) opinion, could adversely affect the safety of the participant. Participants with history of the following will be excluded: irritable bowel syndrome, menorrhagia, fainting spells or dizzy spells or syncope, chronic abdominal or pelvic pain, hemoptysis, gastric ulcers, or anemia. Transient hemorrhage (e.g., infrequent epistaxis, normal menstrual bleeding, gingival bleeding, hemorrhoidal bleeding, etc.) would not preclude enrollment.
• Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant will comply with the protocol or complete the study per protocol.
• Any surgical or medical condition that could interfere with the absorption, distribution, metabolism, or excretion of the study drug.
• Fever (body temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Admission to the CRU.
• Any acute illness within 30 days prior to Admission to the CRU.
• History of severe allergic or anaphylactic reactions, determined at the discretion of the Investigator.
• Known or suspected intolerance or hypersensitivity to the IP, closely related compounds, or any of the stated ingredients.
• History of malignancy except for non-melanoma skin cancer excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening.
• Abnormal ECG findings at Screening or Admission that are considered by the Investigator to be clinically significant.
• History or presence of a condition associated with significant immunosuppression.
• History of life-threatening infection (e.g., meningitis) within 5 years prior to Screening.
• Infections requiring parenteral antibiotics within the 6 months prior to Screening.
• Vaccination with a live-attenuated vaccine within the 4 weeks prior to Screening through to the EOS.
• Exposure to any significantly immunosuppresive drug (including experimental therapies as part of a clinical trial) within the 4 months prior to Screening or five half-lives, whichever is longer. Topical steroids are allowed at the discretion of the Investigator.
• Positive hepatitis panel (including HBsAg, HBcAb or anti-HCV), or a positive HIV antibody screen.
• A BP value outside the specified range of 90 mm Hg to 160 mmHg (for SBP) and 50 mm Hg to 95 mmHg (for DBP; both inclusive) at Screening or Admission (can be repeated once at Screening at the Investigator’s discretion).
• A history of substance abuse or dependency or history of recreational IV drug use over the last 5 years (by self-declaration).
• Regular alcohol consumption defined as >14 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit, or a 125 mL glass of wine) within 6 months of Screening. Participant is unwilling to abstain from alcohol beginning 48 hours prior to each visit and during the confinement period.
• Regularly consume more than 8 cups (i.e., 2 L) daily of beverage containing caffeine and unable to abstain from caffeine- or xanthine-containing products for at least 24 hours prior to Admission to the CRU and during confinement.
• Currently smoke (including tobacco, marijuana, e-cigarettes, vaping, nicotine gum, etc.) or have used such products within 2 weeks prior to Screening.
• Have undergone major surgery or have donated blood within 12 weeks prior to the start of the study.
• A history of bleeding diathesis or other bleeding disorders.
• Use of any prescription medications/products (other than hormonal contraception: OCPs, long-acting implantable hormones, injectable hormones, vaginal ring, or IUD) within 30 days prior to Screening, unless reviewed and approved by the Investigator in consultation with the Sponsor. Simple analgesia (NSAID or paracetamol) may be permitted at the discretion of the Investigator).
• Use of any OTC, non-prescription preparations (including vitamins, minerals, phytotherapeutic/herbal/plant-derived preparations) within 14 days prior to Admission to the CRU.
• A history of orthostatic hypotension or evidence of orthostatic hypotension at Screening that may make participation in the study inappropriate, as determined by the Investigator or delegate.