Influence of 7-day hospitalization for phase i study on the biochemical laboratory tests of healthy volunteers.

Kanamaru, Mitsutaka; Nagashima, Satoru; Uematsu, Toshihiko; Nakashima, Mitsuyoshi

doi:10.3999/jscpt.20.493

Cited by 25 publications

(19 citation statements)

References 4 publications

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“…Transient liver function test increases are commonly observed with prolonged confinement of study volunteers in phase 1 units. [29][30][31] The influence of diet on liver function tests and serum lipids in healthy male volunteers residing in a phase 1 unit was well described by Purkins et al 31 It is thought that these elevations in liver function tests and triglycerides may be the result of the relative inactivity of the subjects and a change of diet while in the unit. In a Japanese phase 1 study, surplus calories were believed to be the sole cause of elevated transaminases observed in healthy volunteers after 7 days of residence in a phase 1 unit.…”

Section: Discussionmentioning

confidence: 93%

“…None of those were reported as AEs and none were considered to be significant by the investigator. Transient liver function test increases are commonly observed with prolonged confinement of study volunteers in phase 1 units 29 – 31 . The influence of diet on liver function tests and serum lipids in healthy male volunteers residing in a phase 1 unit was well described by Purkins et al 31 It is thought that these elevations in liver function tests and triglycerides may be the result of the relative inactivity of the subjects and a change of diet while in the unit.…”

Section: Discussionmentioning

confidence: 95%

“…The influence of diet on liver function tests and serum lipids in healthy male volunteers residing in a phase 1 unit was well described by Purkins et al 31 It is thought that these elevations in liver function tests and triglycerides may be the result of the relative inactivity of the subjects and a change of diet while in the unit. In a Japanese phase 1 study, surplus calories were believed to be the sole cause of elevated transaminases observed in healthy volunteers after 7 days of residence in a phase 1 unit 29 . In our study, all subjects were instructed to avoid strenuous exercise during the 7 days following dosing.…”

Section: Discussionmentioning

confidence: 96%

“…Blood samples for the determination of serum golimumab concentrations were collected 1 hour prior to golimumab administration and 12 hours after administration and on days 2, 3,4,5,6,7,8,11,15,22,29,36,43, and 50. A 5% deviation from the planned PK sampling time was allowable.…”

Section: Blood Sampling and Analysismentioning

confidence: 99%

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Lack of Racial Differences in the Pharmacokinetics of Subcutaneous Golimumab in Healthy Japanese and Caucasian Male Subjects

Ling¹,

Lyn²,

Xu³

et al. 2010

The Journal of Clinical Pharma

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This phase 1 study evaluated the single-dose pharmacokinetics and safety of subcutaneous golimumab, a human anti-tumor necrosis factor-alpha monoclonal antibody, in healthy Japanese and Caucasian subjects. Eligible subjects were males, aged 20 to 45 years, weighing 50 to 90 kg with a body mass index of 19 to 30 kg/m(2). Japanese and Caucasian subjects were matched by body weight and dose group. Blood samples were collected through day 50 following a single subcutaneous injection of golimumab 50 or 100 mg. The pharmacokinetic parameters were determined using a noncompartmental method. All 51 subjects (24 Japanese, 27 Caucasian) were included in the safety analysis; 47 completed the study and were included in the pharmacokinetic analysis. The pharmacokinetics of golimumab were comparable in both race groups. Peak concentrations were observed approximately 4 to 6 days after administration. No significant differences in exposure or mean half-life (range, 11-13 days) were observed between Japanese and Caucasian subjects at the same dose level. Regardless of race, serum golimumab exposure increased with increasing dose. Mean apparent clearance ranged from 12 to 19 mL/kg/d. Mean apparent volume of distribution (224-262 mL/kg) remained constant with an increase in dose. No antibodies to golimumab were detected. Single subcutaneous injections of golimumab 50 mg or 100 mg were generally well tolerated in these healthy male Japanese and Caucasian subjects.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 96%

Section: Blood Sampling and Analysismentioning

confidence: 99%

See 2 more Smart Citations

Lack of Racial Differences in the Pharmacokinetics of Subcutaneous Golimumab in Healthy Japanese and Caucasian Male Subjects

Ling¹,

Lyn²,

Xu³

et al. 2010

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…No subjects in the placebo group had an ALT ≥ 3x ULN. ALT elevation in placebo-treated subjects in phase I trials has been recognized [23][24][25] and is associated with a low-fat and high-carbohydrate diet 24,26) and hospitalization 27) . In this study the diet provided a high proportion of carbohydrates and 20% fat, suggesting that this composition may play a role in ALT variations.…”

Section: Conflicts Of Interestmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Lomitapide in Japanese Subjects

Täubel¹,

Sumeray

Lorch³

et al. 2016

J Atheroscler Thromb

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Aims: Lomitapide is a licensed treatment for patients with homozygous familial hypercholesterolaemia in the USA, the EU, Canada, and Mexico. This study was conducted to compare the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of lomitapide between Japanese and Caucasian subjects with elevated low-density lipoprotein cholesterol (LDL-C) after single and multiple doses. Methods: In this randomized, double-blind, placebo-controlled study, 36 Japanese and 36 Caucasian subjects with LDL-C levels ≥ 110 mg/dL were administered an escalating lomitapide dose range of 10 -60 mg or placebo. Subjects were assessed for safety, tolerability, and lipid levels. Results: Exposure to lomitapide as measured by Cmax was linear and increased over the dose range of 10 -60 mg for both single-and multiple-dose administration. The correlation between AUC0-t and Ctrough demonstrated the lack of differences in the PK of lomitapide among ethnic groups. Lomitapide dose-dependent reductions in lipid parameters were observed and showed no ethnic differences. The safety assessments showed that the main treatment-related side effects identified were increases in hepatic enzymes and that the majority of treatment-related treatment-emergent AEs were gastrointestinal disorders. Conclusions: Lomitapide was effective in reducing LDL-C levels in a dose-dependent manner. Similar PK, efficacy, and safety profiles were observed in Japanese and Caucasian subjects, which suggest no differences in lomitapide activity or metabolism between the two populations compared in this study.J Atheroscler Thromb, 2016; 23: 606-620.

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Phase I Study of Y‐20811, a New Long‐Acting Thromboxane Synthetase Inhibitor by Oral Administration

Nakashima

Takiguchi

Mizuno

et al. 1989

The Journal of Clinical Pharma

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The safety, pharmacological action and pharmacokinetics of the thromboxane (TX) synthetase inhibitor Y-20811, a prospective medication for ischemic vascular disorder, were investigated in Phase I clinical trials in which single and repeated doses were administered orally to 32 healthy adult male volunteers. In the single-dose study, subjects were given single doses of 2.5, 5, 10, 25, 50, and 100 mg; in the repeated-dose study, a single dose of 50 mg was administered daily for 5 days. In the repeated-dose study, slight elevation of liver function test parameters in 1 subject was observed, but throughout the trials, no abnormality attributable to the test drug was found in other routine laboratory tests, subjective and objective findings, vital signs (blood pressure, pulse rate, body temperature, respiration rate), ECG, or bleeding time; nor did any finding indicate a problem concerning the safety of Y-20811. In both single- and repeated-dose studies, inhibition of the serum TXB2 production and an increase in the 6-keto-prostaglandin F1 alpha production during whole-blood coagulation, and inhibition of arachidonic acid-induced platelet aggregation were observed from 1 hour after administration of Y-20811. The duration of these actions was long, the former two lasting 168 hours (1 week) and the latter 48-72 hours or more. Slight inhibition of adenosine diphosphate-induced secondary platelet aggregation was also observed. The maximum plasma concentration time (tmax) of Y-20811 was 0.5-1.1 hours. The initial-phase half-life (t1/2 alpha) was 0.8-1.1 hours and the final-phase half-life (t1/2 beta) was 4.7-9.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

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Influence of 7-day hospitalization for phase i study on the biochemical laboratory tests of healthy volunteers.

Cited by 25 publications

References 4 publications

Lack of Racial Differences in the Pharmacokinetics of Subcutaneous Golimumab in Healthy Japanese and Caucasian Male Subjects

Lack of Racial Differences in the Pharmacokinetics of Subcutaneous Golimumab in Healthy Japanese and Caucasian Male Subjects

Pharmacokinetics and Pharmacodynamics of Lomitapide in Japanese Subjects

Phase I Study of Y‐20811, a New Long‐Acting Thromboxane Synthetase Inhibitor by Oral Administration

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