scholarly journals First‐in‐human studies of MW01‐6‐189WH, a brain‐penetrant, anti‐neuroinflammatory, small molecule drug candidate: Phase 1 safety, tolerability, pharmacokinetic, and pharmacodynamic studies in healthy adult volunteers

2020 ◽  
Vol 16 (S9) ◽  
Author(s):  
Linda J. Van Eldik ◽  
Saktimayee M. Roy ◽  
Jeffrey T. Guptill
Keyword(s):  
Small Molecule ◽  
Healthy Adult ◽  
Phase 1 ◽  
Human Studies ◽  
Drug Candidate ◽  
Small Molecule Drug ◽  
Adult Volunteers

scholarly journals A Phase 1 Study of a Recombinant Viruslike Particle Vaccine against Human Papillomavirus Type 11 in Healthy Adult Volunteers

2001 ◽  
Vol 183 (10) ◽  
pp. 1485-1493 ◽  
Author(s):  
Thomas G. Evans ◽  
William Bonnez ◽  
Robert C. Rose ◽  
Scott Koenig ◽  
Lisa Demeter ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Healthy Adult ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Viruslike Particle ◽  
Adult Volunteers

Phase 1 study of the PSMA-targeted tubulysin small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 2586-2586
Author(s):  
Michael J. Morris ◽  
Daniel Peter Petrylak ◽  
A. Oliver Sartor ◽  
Nicholas J. Vogelzang ◽  
Michael Groaning ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Small Molecule ◽  
Phase 1 ◽  
Phase 1 Study ◽  
Drug Conjugate ◽  
Small Molecule Drug ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals Phase 1 Safety and Pharmacokinetic Study of Chimeric Murine-Human Monoclonal Antibody cαStx2 Administered Intravenously to Healthy Adult Volunteers

2005 ◽  
Vol 49 (5) ◽  
pp. 1808-1812 ◽  
Author(s):  
Thomas C. Dowling ◽  
Pierre A. Chavaillaz ◽  
David G. Young ◽  
Angela Melton-Celsa ◽  
Alison O'Brien ◽  
...  
Keyword(s):  
Shiga Toxin ◽  
Healthy Adult ◽  
Phase 1 ◽  
Human Monoclonal Antibody ◽  
Dose Range ◽  
Volume Of Distribution ◽  
Pharmacokinetic Studies ◽  
Human Antibody ◽  
Chimeric Mouse ◽  
Adult Volunteers

ABSTRACT Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated cαStx2, that has neutralizing activity in a mouse model was produced and tested in healthy adult volunteers. In this phase I dose escalation study, cαStx2 was generally well tolerated. Pharmacokinetic studies indicated that clearance was stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 ± 0.023 ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 ± 0.078 ml/kg/h), suggesting saturable elimination. A similar nonlinear trend was observed for the volume of distribution, where average values ranged from 0.064 ± 0.015 liter/kg for the 1.0- to 10-mg/kg doses and 0.043 ± 0.005 for the 0.01-mg/kg dose. The relatively small volume of distribution suggests that the antibody is limited to the vascular (plasma) compartment. The mean half-life was 165 ± 66 h, with lowest values observed for the 0.1-mg/kg dose (56.2 ± 9.7 h) and the highest values reported for the 10.0-mg/kg dose (206.4 ± 12.4 h). Future studies are needed to confirm the safety of this cαStx2, and innovative clinical trials will be required to measure its efficacy in preventing or treating HUS.

scholarly journals Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Amanda M. Healan ◽  
J. McLeod Griffiss ◽  
Howard M. Proskin ◽  
Mary Ann O'Riordan ◽  
Wesley A. Gray ◽  
...  
Keyword(s):  
Steady State ◽  
Healthy Adult ◽  
Controlled Trial ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Parameter Estimates ◽  
Open Label ◽  
Combination Drug ◽  
Period 2 ◽  
Adult Volunteers

ABSTRACT Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP synthase. Bedaquiline has been used to effectively treat tuberculosis (TB) caused by drug-susceptible and drug-resistant Mycobacterium tuberculosis. Rifamycins are a cornerstone of combination drug regimens for the treatment of TB. This phase 1, open-label, randomized, controlled trial evaluated the effect of steady-state dosing of rifabutin or rifampin on the safety, tolerability, and pharmacokinetics of bedaquiline given as a single dose. Thirty-three healthy subjects were enrolled to receive a 400-mg single oral dose of bedaquiline at two time points, on study days 1 and 29. Subjects were randomly assigned to once daily oral doses of rifabutin (300 mg/day, n = 17) or rifampin (600 mg/day, n = 16) during period 2 from days 20 to 41. Serial blood sampling for bedaquiline measurement occurred on days 1 and 29 through 336 h after bedaquiline administration. The day 29 bedaquiline pharmacokinetic parameter estimates were compared to the corresponding day 1 estimates for each rifamycin group. Steady-state rifampin reduced bedaquiline AUC0–336 approximately 45%, from 47.69 h·μg/ml in period 1 to 26.33 h·μg/ml in period 2. Bedaquiline apparent clearance accelerated 24% in rifampin-treated subjects from 6.59 liters/h in period 1 to 8.19 liters/h in period 2. Steady-state rifabutin resulted in little quantitative impact on bedaquiline exposure but was associated with grade 3 and 4 adverse events before and after the day 29 bedaquiline dose. Dosage adjustments may therefore be necessary to ensure that bedaquiline plasma concentrations reach therapeutic levels safely when combining bedaquiline and rifamycins in TB treatment regimens. (This single-site, randomized, open-label, prospective study in healthy adult volunteers was registered at Clinicaltrials.gov under registration no. NCT01341184.)

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