Safety, tolerability, and pharmacokinetics of BMS-986263/ND-L02-s0201, a novel targeted lipid nanoparticle delivering HSP47 siRNA, in healthy participants: A randomised, placebo-controlled, double-blind, phase 1 study

Objective.This phase I study aimed to systematically assess the safety, local tolerability, pharmacokinetics, and preliminary efficacy of topical icotinib hydrochloride cream in patients with mild to moderate plaque psoriasis.Materials and Methods.Eligible Chinese adult patients with mild to moderate psoriasis were assigned to the icotinib cream or vehicle group. Icotinib cream with increasing concentrations (0.5%, 1.0%, 2.0%, and 4.0%) or vehicle were administered by the fingertip unit method to the skin lesions twice a day for 4 weeks. Safety assessments included the incidence and severity of adverse events (AEs), local tolerability at the treatment area, vital signs, and laboratory examinations. Plasma levels of icotinib were also measured for the pharmacokinetics calculation. The efficacy was preliminarily explored by assessing the improvement in the severity level using Target Plaque Severity Score (TPSS) and overall improvement using the Psoriasis Area Severity Index (PASI) and Dermatological Quality Life Index.Results.Forty-one patients were enrolled and qualified for safety analysis. 27 (65.9%) patients experienced at least one AE, of which application-site adverse drug reactions (ADRs) were reported in 6 (14.6%) patients. All ADRs were of grade 1 or 2, most common irritation (4.5%), itching (3.1%), and erythema (2.4%), and resolved during follow-up. The systemic exposure to icotinib was very low; the highest plasma concentration was 0.214 ng/mL, while the area under the curve from 0 to 12 hours was 1.626 h·ng/mL. The TPSS improved for all icotinib groups after treatment in a dose- and time-dependent manner.Conclusion.This phase 1 study demonstrated favorable safety, tolerable toxicity, and preliminary efficacy of icotinib cream in patients with mild to moderate psoriasis. The dose concentration of 2.0% (twice daily based on the fingertip unit method) is recommended for further study.Study Design.This is a single-center, randomized, double-blind, and vehicle-controlled study.

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Safety, tolerability and pharmacodynamics of AZP-3601, a novel long-acting PTH analog, in healthy adults: Data from a randomized, double-blind, placebo-controlled phase 1 study

Endocrine Abstracts ◽

10.1530/endoabs.73.oc6.5 ◽

2021 ◽

Author(s):

Soraya Allas ◽

Michel Ovize ◽

Michael D. Culler ◽

Clarisse Geraul ◽

van de Wetering Jeroen ◽

...

Keyword(s):

Phase 1 ◽

Healthy Adults ◽

Phase 1 Study ◽

Double Blind ◽

Double Blind Placebo ◽

Long Acting

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A phase 1 study to assess potential interaction between ASP8062 and alcohol in healthy adult subjects

Journal of Psychopharmacology ◽

10.1177/02698811211058967 ◽

2022 ◽

pp. 026988112110589

Author(s):

Mototsugu Ito ◽

Anna Spence ◽

Mary Beth Blauwet ◽

Nakyo Heo ◽

Ronald Goldwater ◽

...

Keyword(s):

Phase 1 ◽

Pharmacokinetic Interaction ◽

Opioid Use Disorder ◽

Potential Interaction ◽

Analysis Of Covariance ◽

Opioid Use ◽

Phase 1 Study ◽

Double Blind ◽

Pharmacodynamic Interaction ◽

Crossover Phase

Background: ASP8062 is a novel orally active GABAB receptor positive allosteric modulator in clinical development for the treatment of alcohol use disorder (AUD) and opioid use disorder (OUD). Aims: This study assessed the potential pharmacokinetic/pharmacodynamic interaction between ASP8062 and alcohol under single-dose conditions in healthy adults. Methods: A double-blind, placebo-controlled, crossover phase 1 study was conducted in which 20 subjects were randomly assigned to four treatment sequences (ASP8062 + alcohol; ASP8062 + placebo alcohol; placebo + alcohol; placebo + placebo alcohol) each consisting of four treatment periods, separated by washout periods of at least 14 days. An analysis of variance was used to assess pharmacokinetic interaction and a mixed-effects analysis of covariance was used to assess pharmacodynamic interaction. Results/outcomes: After administration of alcohol, a mild to minimal increase in plasma exposure (AUCinf and Cmax) of ASP8062 was observed, but tmax and t½ for ASP8062 remained unchanged after administration of alcohol. In contrast, ASP8062 did not affect the AUClast and Cmax of ethanol. No clinically relevant differences in cognition measurements were observed with ASP8062 compared with placebo, but there were expected impairments in psychomotor and executive function with alcohol alone. ASP8062 in combination with alcohol resulted in worse scores in cognition measurements than alcohol alone, but this potentiation was not consistent. ASP8062 administered alone was safe and well-tolerated and safety findings in subjects administered alcohol alone were not augmented when ASP8062 was administered in combination with alcohol. Conclusion/interpretation: The data support further clinical studies investigating ASP8062 in patients with AUD.

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