Does a food intervention makes abiraterone treatment affordable?

e16523 Background: Abiraterone is registered for metastatic prostate cancer. It is used in a fixed oral dose of 1000mg OD in a fasted state in combination with 10mg prednisone daily. Although large differences in the effect of food on abiraterone exposure are reported (ranging from 1-10 fold increase in area under the concentration time curve (AUC)) it is generally accepted that abiraterone is much better absorbed in the presence of food. By administering abiraterone with food a reduced dose can be given while maintaining equivalent abiraterone exposure. Moreover aadministering abiraterone with food is more patient friendly and it could significantly reduce the treatment costs of abiraterone.The aim of this study was to establish the bio-equivalent lower dose of abiraterone when taken with a continental breakfast compared to the standard intake of 1000mg OD in fasted state. Methods: In this phase I cross-over multi-center study abiraterone pharmacokinetics (PK) were evaluated in patients with metastatic prostate cancer who were treated with 1000 mg abiraterone in a fasted state, followed by 500 mg taken with a continental breakfast. After both periods of 14 days, abiraterone plasma exposure was measured. Bioequivalence was assumed when the GMR (fed/fasted) of the AUC0-24h and Cmax and their 90% confidence interval (CI) were within the range of 0.8 and 1.7. Results: 14 patients were enrolled into the study, of whom 12 were eligible for PK analysis. GMR (fed/fasted) AUC0-24h was 0.88 (90% CI 0.73-1.07), GMR Cmax was 1.03 (CI 0.79-1.34) and the GMR of Ctrough was 0.81 (90% CI 0.60-1.10). Conclusions: Ingesting 500mg abiraterone with a continental breakfast was not considered bio-equivalence when compared to 1000mg taken fasted. The criteria for bio-equivalence could not be met due to the large variability in pharmacokinetics of abiraterone within and between patients. Due to this large variability in abiraterone exposure, we believe that dose optimization by food intake is not a feasible strategy for abiraterone. The intake of abiraterone with food could not be advised based on the results presented in our study. Clinical trial information: NCT02883166. [Table: see text]

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A study of two ODM-201 formulations with a safety and tolerability extension phase in patients with metastatic chemotherapy-naive castration-resistant prostate cancer (CRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.115 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 115-115 ◽

Cited By ~ 2

Author(s):

Christophe Massard ◽

Teuvo L. J. Tammela ◽

Egils Vjaters ◽

Vilnis Lietuvietis ◽

Petri Bono ◽

...

Keyword(s):

Prostate Cancer ◽

Response Rate ◽

Specific Antigen ◽

Castration Resistant Prostate Cancer ◽

Capsule Formulation ◽

Castration Resistant ◽

Psa Response ◽

Effect Of Food ◽

Extension Period ◽

Clinical Trial Information

115^ Background: This open phase I trial assessed the bioavailability, and the effect of food on the bioavailability of ODM-201 600mg tablets compared to a 600mg capsule formulation. Efficacy, safety, and tolerability of ODM-201 were studied in the extension period. Methods: The study had two parts: a pharmacokinetic (PK), and a safety and tolerability part. Dosing was 600mg bid with or without food. In the PK part, three single doses of ODM-201 were given over 3 weeks. In the extension part patients could continue treatment until disease progression or until an intolerable adverse event or condition that prevented further dosing of ODM-201. Results: Thirty men with metastatic chemotherapy-naïve castration-resistant prostate cancer (CRPC) were enrolled, the median age was 68. The median prostate-specific antigen (PSA) was 18.2 ng/mL and testosterone 23.1 ng/dL at baseline. Food interaction was observed when ODM-201 formulations were administered after a high fat content breakfast compared to administration at fast. AUC and Cmaxvalues were about 50% lower after fast. Twenty nine patients have completed the 4-week visit. The PSA response rate (50% or more PSA decline) was 86%, with a median PSA decrease of -66% (-96, 5) at week 4 (N=18/21). Most commonly reported adverse events so far are fatigue, abdominal pain, diarrhea, hematuria, and nausea. Conclusions: ODM-201 600mg bid as tablets has comparable PK to capsules used in the phase II ARADES trial. It is well tolerated and has good PSA response in chemotherapy-naïve patients with CRPC . Clinical trial information: NCT01784757.

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Effects of Food and Omeprazole on a Novel Formulation of Super Bioavailability Itraconazole in Healthy Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01723-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 4

Author(s):

Julian Lindsay ◽

Stuart Mudge ◽

George R. Thompson

Keyword(s):

Steady State ◽

Maximum Concentration ◽

Healthy Adults ◽

Plasma Exposure ◽

Open Label ◽

Time Curve ◽

Dosing Interval ◽

Fasted State ◽

Concentration Time ◽

Bioavailability Study

ABSTRACT To address the limited bioavailability and intolerance of the conventional itraconazole (ITZ) formulations, a new formulation labeled super bioavailability (SUBA) itraconazole has been developed; however, the specific effects of food and gastric pH are unknown. This study evaluated the pharmacokinetic profile of SUBA itraconazole under fasting and fed conditions, as well as with the concomitant administration of a proton pump inhibitor. First, the effect of food was assessed in an open-label, randomized, crossover bioavailability study of 65-mg SUBA itraconazole capsules (2 65-mg capsules twice a day) in healthy adults (n = 20) under fasting and fed conditions to steady-state levels. Second, an open-label, two-treatment, fixed-sequence comparative bioavailability study in healthy adults (n = 28) under fasted conditions compared the pharmacokinetics of a single oral dose of SUBA itraconazole capsules (2 65-mg capsules/day) with and without coadministration of daily omeprazole delayed-release capsules (1 40-mg capsule/day) under steady-state conditions. In the fed and fasted states, SUBA itraconazole demonstrated similar concentrations at the end of the dosing interval, with modestly lower total and peak ITZ exposure being shown when it was administered under fed conditions than when it was administered in the fasted state, with fed state/fasted state ratios of 78.09% (90% confidence interval [CI], 74.49 to 81.86%) for the area under the concentration-time curve over the dosing interval (14,183.2 versus 18,479.8 ng · h/ml), 73.05% (90% CI, 69.01 to 77.33%) for the maximum concentration at steady state (1,519.1 versus 2,085.2 ng/ml), and 91.53% (90% CI, 86.41 to 96.96%) for the trough concentration (1,071.5 versus 1,218.5 ng/ml) being found. When dosed concomitantly with omeprazole, there was a 22% increase in the total plasma exposure of ITZ, as measured by the area under the concentration-time curve from time zero to infinity (P = 0.0069), and a 31% increase in the peak plasma exposure of ITZ, as measured by the maximum concentration (P = 0.0083).

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Effects of Food on the Relative Bioavailability of Lapatinib in Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.3285 ◽

2009 ◽

Vol 27 (8) ◽

pp. 1191-1196 ◽

Cited By ~ 81

Author(s):

Kevin M. Koch ◽

Nandi J. Reddy ◽

Roger B. Cohen ◽

Nancy L. Lewis ◽

Bonnie Whitehead ◽

...

Keyword(s):

Systemic Exposure ◽

Random Order ◽

Relative Bioavailability ◽

High Fat ◽

Low Fat ◽

Time Curve ◽

Fed State ◽

Fasted State ◽

Concentration Time ◽

Effect Of Food

Purpose This study was conducted to characterize the effect of food on the relative bioavailability of lapatinib. Patients and Methods A single 1,500-mg, oral dose of lapatinib was administered to 27 patients with advanced solid tumors on each of three occasions that were 1 week apart, in random order: after an overnight fast, with a low-fat breakfast, and with a high-fat breakfast. Results The low-fat breakfast produced mean increases in lapatinib area under the concentration-time curve (AUC) of 167% (2.67-fold) and maximum concentration (Cmax) of 142% (2.42-fold). The high-fat breakfast produced mean increases in lapatinib AUC of 325% (4.25-fold) and Cmax of 203% (3.03-fold) compared with the fasted state. Increased bioavailability in the fed state did not significantly decrease relative variability. Therefore, absolute variability in systemic exposure was increased. Conclusion These large increases in lapatinib bioavailability and absolute variability support the recommendation for dosing in the fasted state to achieve consistent therapeutic exposure. Prescribers and patients should consider the potential consequences of toxicity or diminished efficacy that might result from dosing without regard to variations in diet.

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Pathologic correlation of 89Zr-Df-IAB2M antiprostate-specific membrane antigen (PSMA) minibody in patients with metastatic prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.220 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 220-220 ◽

Cited By ~ 1

Author(s):

Michael J. Morris ◽

Stephen Barnett Solomon ◽

Jeremy C. Durack ◽

Joseph A. O' Donoghue ◽

Serge K. Lyashchenko ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Blood Pool ◽

Whole Body ◽

Bone Lesions ◽

Pet Ct ◽

Pathologic Findings ◽

High Concordance ◽

Specific Membrane ◽

Clinical Trial Information

220 Background: IAB2M is a novel anti-PSMA minibody (Mb) based on the humanized J591 antibody that targets the extracellular domain of PSMA. The Mb has been engineered to remove Fc-Rn interactions and reduce the molecular weight relative to J591. The result is faster blood pool clearance, for a more favorable imaging schedule, while retaining bivalent targeting of PSMA. We have previously reported on the pharmacokinetics, dosimetry, and lesion uptake of IAB2M(Pandit-Taskar et al, WMIS 2014). Here we report the correlation between imaging and pathology of biopsies of PSMA avid lesions. Methods: Following standard imaging (SI) of CT/MRI, bone scintigraphy (BS), and FDG PET, 5 mCi of 89Zr-Df-IAB2M was administered intravenously. Escalating minibody doses of 10, 20, and 50 mg were delivered, with cohort expansion at 10 and 20 mg. Whole body PET/CT scans were serially performed at various time points:1-2 h, 24 h, 48 h, and 72-144 h post injection. Metastases identified on PET were confirmed, where possible, with bx’s in the following preference: concordant IAB2M and FDG positivity, IAB2M, and FDG mismatch, or a mismatch between SI and any PET. Results: 24 patients (pts) with metastatic prostate cancer were scanned (11 at 10, 7 at 20, and 6 at 50 mg Mb doses). A total of 15 bxs (7 soft tissue, 8 bone) were performed on 14 pts; the histopathologic correlation is summarized in the table below. 13 lesions were identified by IAB2M, 11 by FDG, and 14 by SI. Of these, 12/13 (92.3%), 10/11 (90.9%), 12/14 (85.7%) were biopsy positive for cancer, respectively. 2 bone lesions were not identified by IAB2M, evident on other imaging modalities, and were both neg by bx. Overall bx concordance (pos/pos, neg/neg) with imaging was: IAB2M 14/15 (93%) vs. BS/CT 13/15 (86%) vs. FDG 12/15 (80%). Conclusions: An ongoing analysis of IAB2M imaging showed a high concordance with pathologic findings in patients with metastatic prostate cancer. Clinical trial information: NCT01923727. [Table: see text]

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Effect of food on exposure to napabucasin: Data from two phase I studies.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.477 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 477-477

Author(s):

Xiaoshu Dai ◽

Naoto Noda ◽

Yuran Xie ◽

Bo Xu ◽

Matthew Hitron ◽

...

Keyword(s):

Two Phase ◽

Fed State ◽

Investigational Agent ◽

Fasted State ◽

Japanese Male ◽

Advanced Malignancies ◽

The Us ◽

Effect Of Food ◽

Clinical Trial Information ◽

Japanese Diet

477 Background: Napabucasin is an orally-administered NAD(P)H quinone dehydrogenase 1–bioactivatable investigational agent hypothesized to affect multiple oncogenic cellular pathways including STAT3. Methods: Food effects on napabucasin pharmacokinetics were evaluated in two studies: one at two sites in Japan (Study 1; JapicCTI-205447) and the other at two sites in the US and three in Canada (Study 2; NCT01775423). Study 1 enrolled healthy Japanese male volunteers (HJMV) who received napabucasin 480 mg (formula 2) per sequential design — fasting on Day (D) 1 followed by a Japanese diet (JD) on D8 — with a 6-D intervening washout. In Study 2, patients (pts) with advanced malignancies received napabucasin 500 mg (formula 1) on D1 in the fasted state, then napabucasin 500 mg (formula 2) on D4 and D8 with a high-fat breakfast [HFB] or in the fasted state per the randomized sequence per crossover design. Results: In Study 1, mean plasma napabucasin levels 6–10 h after napabucasin 480 mg administration were higher in fed (JD) vs fasted states; in the fed state, Cmax increased by 15% and AUClast by ~60% (Table), while tmax decreased by ~1.4 hours. Adverse events (AEs) in Study 1 occurred in 5/6 (83.3%) HJMVs (fasted, n=3; fed, n=5; all grade [gr] 1). In Study 2, mean concentration profiles were comparable in fasted and fed (HFB) states for napabucasin 500 mg. When comparing fasted and fed states, Cmax increased by 21% and AUClast by 39% in the fed state (Table). Interpatient variability was high: geometric CV% for CL/F was 75.9% (fed) and 141% (fasted). AEs in Study 2 occurred in 68% (17/25) of fasted pts (gr 1: n=7; gr 2: n=8; gr 3, n=2) and 50% (7/14) of pts fed an HFB (gr 1: n=2; gr 2: n=3; gr 3, n=2). Conclusions: In HJMVs, napabucasin 480 mg administered with a JD increased exposure (Cmax; AUClast; AUCinf) and decreased tmax vs the fasted state. In pts with advanced malignancies, napabucasin 500 mg administered with an HFB increased exposure (Cmax; AUClast) vs the fasted state. These exposure increases are not considered to be of clinical relevance. Clinical trial information: JapicCTI-205447; NCT01775423. [Table: see text]

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Effect of Food on the Pharmacokinetics of the Integrase Inhibitor Dolutegravir

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05739-11 ◽

2011 ◽

Vol 56 (3) ◽

pp. 1627-1629 ◽

Cited By ~ 62

Author(s):

Ivy Song ◽

Julie Borland ◽

Shuguang Chen ◽

Parul Patel ◽

Toshihiro Wajima ◽

...

Keyword(s):

Single Dose ◽

Healthy Subjects ◽

Integrase Inhibitor ◽

High Fat ◽

Time Curve ◽

Clinical Safety ◽

Fasted State ◽

Concentration Time ◽

Rate Of Absorption ◽

Effect Of Food

ABSTRACTHealthy subjects received dolutegravir at 50 mg in a single-dose crossover study while they were in the fasted state or with low-, moderate-, or high-fat meals. Food increased dolutegravir exposure and reduced the rate of absorption. The area under the concentration-time curve from 0 h to infinity (AUC0–∞) increased by 33%, 41%, and 66% when administered with low-, moderate-, or high-fat meals, respectively, compared with fasting. This increase in dolutegravir exposure is not anticipated to impact clinical safety, and therefore dolutegravir can be taken with or without food and without regard to fat content.

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