scholarly journals A randomized, double-blind, single-dose study (LAVENDER) to assess the safety, tolerability, pharmacokinetics, and immunogenicity of a combined infusion of ABP 980 and pertuzumab in healthy subjects

2021 ◽  
Author(s):  
Vladimir Hanes ◽  
Vincent Chow ◽  
Tina Stewart ◽  
Adeep Puri
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Pharmacokinetic Parameters ◽  
Single Infusion ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Single Dose Study ◽  
Parallel Group ◽  
Dose Study ◽  
Cardiac Disorders

Abstract Purpose ABP 980 (KANJINTI™) is a biosimilar to reference product HERCEPTIN® (trastuzumab RP). The goal of this study was to characterize the safety, tolerability, and immunogenicity of ABP 980 plus pertuzumab (PERJETA®) when co-administered in a single infusion bag in healthy subjects. Methods This randomized, double-blind, single-dose, 2-arm, parallel-group study (LAVENDER Study) evaluated an intravenous (IV) infusion of ABP 980 (6 mg/kg) plus pertuzumab (420 mg) combined in a single infusion bag relative to an IV infusion of trastuzumab RP (6 mg/kg) plus pertuzumab (420 mg) combined in a single infusion bag given over 60 min. The subjects were followed for 92 days post dosing. Results A total of 42 subjects were enrolled in the study and treated with investigational product. Due to an operational issue during dosing, the first 6 subjects enrolled in the study were replaced. A total of 36 randomized subjects, n = 18 for ABP 980 plus pertuzumab and n = 18 for trastuzumab RP plus pertuzumab, were treated. Resulting serum concentrations of ABP 980 and trastuzumab RP were similar. There were no serious adverse events, no deaths, and no cardiac disorders during the study. No subject developed anti-drug antibodies throughout the study. Conclusions This study demonstrated the safety and tolerability of ABP 980 and pertuzumab admixture in a single infusion bag. The safety profiles and pharmacokinetic parameters of ABP 980 and pertuzumab were consistent with what is known for trastuzumab RP and pertuzumab. Clinical trial listing EudraCT 2018-002903-33.

scholarly journals Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects

2009 ◽  
Vol 53 (9) ◽  
pp. 3720-3725 ◽  
Author(s):  
Ann M. Ginsberg ◽  
Martino W. Laurenzi ◽  
Doris J. Rouse ◽  
Karl D. Whitney ◽  
Melvin K. Spigelman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Dose ◽  
Healthy Subjects ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Blood Levels ◽  
Drug Resistant ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study

ABSTRACT PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic Mycobacterium tuberculosis. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support the investigation of this novel compound for the treatment of tuberculosis.

scholarly journals Pharmacokinetics, safety and tolerability of L-3-n-butylphthalide tablet after single and multiple oral administrations in healthy Chinese volunteers

2015 ◽  
Vol 51 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Meng Wang ◽  
Quan-ying Zhang ◽  
Wen-yan Hua ◽  
Ming Huang ◽  
Wen-jia Zhou ◽  
...  
Keyword(s):  
Single Dose ◽  
Multiple Dose ◽  
Compartmental Analysis ◽  
Pharmacokinetic Parameters ◽  
Double Blind ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study ◽  
Repeated Doses ◽  
Healthy Chinese

L-3-n-butylphthalide (L-NBP) is a naturally occurring antioxidant, which can be used for the treatment of acute ischemic stroke and vascular dementia. This study evaluated the safety, tolerability and pharmacokinetics of L-NBP tablets in healthy Chinese volunteers. This was a single-center, randomized, double-blind, placebo-controlled, single- and multiple-dose study. Subjects were assigned to receive a single dose of L-NBP tablet at either 80, 160, 320, or 480 mg (n=40), or multiple doses of 160 mg twice daily for 7 days (n=12). Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of L-NBP were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration; AEs in this study occurred less frequently and more mildly than AEs listed for the DL-NBP soft capsule. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 1 h, and the mean t1/2 was approximately 13.76 h. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 160 to 480 mg. In the multiple-dose study, the steady-state was reached within 3 days with slight accumulation. In summary, the L-NBP tablet was well tolerated in healthy Chinese subjects. Slight accumulation appeared after repeated doses.

scholarly journals Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects

2012 ◽  
Vol 52 (4) ◽  
pp. 1381-1391 ◽  
Author(s):  
Malkanthi Evans ◽  
Mareike Beck ◽  
James Elliott ◽  
Stephane Etheve ◽  
Richard Roberts ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Double Blind ◽  
Single Dose Study ◽  
Dose Study

Results of a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study comparing the fixed combination of acetaminophen, acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of patients with severe migraine

Cephalalgia ◽  
2014 ◽  
Vol 34 (13) ◽  
pp. 1070-1078 ◽  
Author(s):  
Jerome Goldstein ◽  
Martina Hagen ◽  
Morris Gold
Keyword(s):  
Single Dose ◽  
Pain Relief ◽  
Acetylsalicylic Acid ◽  
Acute Treatment ◽  
Fixed Combination ◽  
Double Blind ◽  
Single Dose Study ◽  
Parallel Group ◽  
Dose Study ◽  
Severe Migraine

Introduction In a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study ( n = 1555), a fixed combination of acetaminophen 500 mg, acetylsalicylic acid 500 mg, and caffeine 130 mg (AAC) was compared with ibuprofen 400 mg (IB) and placebo (PLA) for acute treatment of migraine. Subjects and methods An exploratory post-hoc analysis compared AAC with IB and PLA in the subset of patients with severe pain at baseline ( n = 660). Results At most time points, AAC and IB relieved the pain and associated symptoms of severe migraine significantly better than PLA ( p ≤ 0.05). AAC was significantly superior to IB for pain relief at 45 minutes and at one, two, three, and four hours postdose ( p < 0.04); pain intensity difference from one hour through three hours ( p < 0.05); headache response at two hours ( p = 0.04); functional disability reduced to little or none at three hours ( p = 0.013); freedom from phonophobia at three hours ( p = 0.04) and photophobia at 15 minutes postdose ( p = 0.03); and use of rescue medication ( p = 0.018). AAC patients also reported meaningful pain relief 16 minutes faster than IB patients (132 minutes vs 148 minutes, p = 0.026). Conclusions In patients with severe baseline migraine pain, AAC and IB are significantly more effective than PLA, and AAC provides significantly faster and more effective pain relief than IB.

scholarly journals A Randomized, Double-Blind, Single-Dose Study Comparing the Biosimilarity of HOT-1010 With Bevacizumab (Avastin®) in Chinese Healthy Male Subjects

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Huang ◽  
Linling Que ◽  
Ying Ding ◽  
Nannan Chu ◽  
Zhenzhong Qian ◽  
...  
Keyword(s):  
Single Dose ◽  
Adverse Events ◽  
Geometric Mean ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Single Dose Study ◽  
Male Subjects

Objective: This study was conducted to compare the pharmacokinetics, safety and immunogenicity of HOT-1010 with bevacizumab (Avastin®) in Chinese healthy male subjects.Methods: A single-center, randomized, double-blind, single-dose, parallel trial was performed in 84 Chinese healthy male subjects who randomly (1:1) received a single intravenous infusion of 1 mg/kg HOT-1010 or Avastin® for 90 min and followed up for 85 days. Serum concentrations of bevacizumab were analyzed by enzyme-linked immunosorbent assay. Primary pharmacokinetic parameters, Cmax, AUC0-t and AUC0-∞, were calculated and evaluated the bioequivalence between HOT-1010 and Avastin®, the safety and immunogenicity of investigational drugs were also assessed.Results: A total of 82 subjects completed the study. The 90% Confidence Intervals for geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 91.81–103.64%, 85.19–95.39% and 85.04–95.36%, which were all within the bioequivalence margin. Treatment-emergent adverse events were reported in 27 (65.9%) subjects in HOT-1010 group and 23 (56.1%) subjects in Avastin® group. Most TEAEs were mild or moderate. No TEAEs, Serious Adverse Events or deaths leading to discontinuation was reported. Subjects were all tested negative for Anti-drug Antibody.Conclusion: HOT-1010 exhibited the similar pharmacokinetics, safety and immunogenicity profiles of bevacizumab (Avastin®) in Chinese healthy male subjects.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/index.html, CTR20181610.

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