Trial Outcomes & Findings for A Study to Investigate the Effect of Food on Pharmacokinetics of Total EPA and Total DHA of AZD0585 in Healthy Male Japanese Subjects (NCT NCT02372344)

Last Updated: 2016-05-16

Results Overview

To investigate the effect of food timing on PK (area under the plasma concentration-time curve from time zero to infinity \[AUC\]) of single dose of 4 g AZD0585 in healthy male Japanese by assessing plasma concentrations of total eicosapentaenoic acid (EPA) and total docosahexaenoic acid (DHA), and PK parameters over time under the three proposed conditions (fasting, before meal, and after meal).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

72 participants

Primary outcome timeframe

Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

Results posted on

2016-05-16

Participant Flow

The enrollment period started 4 March 2015 and the last subject last visit was 12 May 2015. This was a 3-period crossover study with a minimum 10-day washout period between each treatment visit (Period 1=Visit 2; Period 2=Visit 3; Period 3=Visit 4).

Subjects were randomized to 3 sequences (ABC, BCA or CAB; A=fasting, B=before meal, C=after meal) with a 1:1:1 ratio. 72 subjects were enrolled; 42 randomized and 30 excluded (8 did not fulfil eligibility criteria and 22 refused participation).

Participant milestones

Participant milestones
Measure	Sequence ABC Subjects randomized to treatment sequence ABC: A=fasting / B=before meal / C=after meal. Following an overnight fast of at least 10 hours, a single oral dose of 4 g AZD0585 was administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.	Sequence BCA Subjects randomized to treatment sequence BCA: B=before meal / C=after meal / A=fasting. Following an overnight fast of at least 10 hours, a single oral dose of 4 g AZD0585 was administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.	Sequence CAB Subjects randomized to treatment sequence CAB: C=after meal / A=fasting / B=before meal. Following an overnight fast of at least 10 hours, a single oral dose of 4 g AZD0585 was administered on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions.
Period 1 (Visit 2) STARTED	14	14	14
Period 1 (Visit 2) COMPLETED	14	14	14
Period 1 (Visit 2) NOT COMPLETED	0	0	0
Period 2 (Visit 3) STARTED	14	14	14
Period 2 (Visit 3) COMPLETED	14	14	14
Period 2 (Visit 3) NOT COMPLETED	0	0	0
Period 3 (Visit 4) STARTED	14	14	14
Period 3 (Visit 4) COMPLETED	14	14	14
Period 3 (Visit 4) NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Investigate the Effect of Food on Pharmacokinetics of Total EPA and Total DHA of AZD0585 in Healthy Male Japanese Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD0585 n=42 Participants All subjects received a single oral dose of 4 g AZD0585 on 3 separate occasions (fasting, before meal, and after meal) in a randomized crossover fashion with different food restrictions. Each dose was administered on Day 1 of each separate treatment period: Period 1=Visit 2; Period 2=Visit 3; Period 3=Visit 4.
Age, Continuous	31.0 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	42 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

Population: The PK set included all healthy subjects in the safety population (ie, who received at least 1 administration of AZD0585 and for whom any post-dose data were available) with at least 1 detectable total EPA and total DHA plasma concentration.

Outcome measures

Outcome measures
Measure	Fasting n=37 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered at the end of a 10-hour fast.	Before Meal n=33 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered before consumption of a low calorie, low-fat breakfast (within 30 minutes before starting food intake).	After Meal n=41 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered after consumption of a low calorie, low-fat breakfast (within 30 minutes after starting food intake).
The Effect of Food Timing (Fasting, Before Meal, and After Meal) on Pharmacokinetics (PK; AUC) of AZD0585 in Healthy Male Japanese. Total EPA (n=37, 33, 41)	2.44 milligram x hour /millilitre (mg⋅h/mL) Geometric Coefficient of Variation 66.8	2.66 milligram x hour /millilitre (mg⋅h/mL) Geometric Coefficient of Variation 80.15	3.80 milligram x hour /millilitre (mg⋅h/mL) Geometric Coefficient of Variation 37.55
The Effect of Food Timing (Fasting, Before Meal, and After Meal) on Pharmacokinetics (PK; AUC) of AZD0585 in Healthy Male Japanese. Total DHA (n=4, 2, 2)	0.299 milligram x hour /millilitre (mg⋅h/mL) Geometric Coefficient of Variation 143	0.444 milligram x hour /millilitre (mg⋅h/mL) Geometric Coefficient of Variation 152	0.617 milligram x hour /millilitre (mg⋅h/mL) Geometric Coefficient of Variation 97.7

PRIMARY outcome

Timeframe: Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

To investigate the effect of food timing on PK (maximum plasma concentration \[Cmax\]) of single dose of 4 g AZD0585 in healthy male Japanese by assessing plasma concentrations of total EPA and total DHA, and PK parameters over time under the three proposed conditions (fasting, before meal, and after meal). Analyses of the outcome measures presented are for baseline-adjusted data for total EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. The geometric mean was calculated as the exponential of the arithmetic mean calculated from data on a log scale.

Outcome measures

Outcome measures
Measure	Fasting n=42 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered at the end of a 10-hour fast.	Before Meal n=42 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered before consumption of a low calorie, low-fat breakfast (within 30 minutes before starting food intake).	After Meal n=42 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered after consumption of a low calorie, low-fat breakfast (within 30 minutes after starting food intake).
The Effect of Food Timing (Fasting, Before Meal, and After Meal) on PK (Cmax) of AZD0585 in Healthy Male Japanese. Total EPA (n=42, 42, 42)	78.5 microgram/millilitre (mcg/mL) Geometric Coefficient of Variation 110 • Interval 10.9 to 271.0	97.1 microgram/millilitre (mcg/mL) Geometric Coefficient of Variation 168 • Interval 6.4 to 386.0	221 microgram/millilitre (mcg/mL) Geometric Coefficient of Variation 34.7 • Interval 72.2 to 378.0
The Effect of Food Timing (Fasting, Before Meal, and After Meal) on PK (Cmax) of AZD0585 in Healthy Male Japanese. Total DHA (n=42, 42, 42)	42.1 microgram/millilitre (mcg/mL) Geometric Coefficient of Variation 84.9 • Interval 11.8 to 157.0	52.4 microgram/millilitre (mcg/mL) Geometric Coefficient of Variation 103 • Interval 9.73 to 178.0	92.6 microgram/millilitre (mcg/mL) Geometric Coefficient of Variation 42.65 • Interval 27.0 to 195.0

PRIMARY outcome

Timeframe: Blood samples were collected from pre-dose (Day -1) up to 72 hours post-dose for each of the separate treatment periods (Visits 2, 3 and 4).

To investigate the effect of food timing on PK (area under the plasma concentration-time curve from time zero to 72 hours \[AUC0-72\]) of single dose of 4 g AZD0585 in healthy male Japanese by assessing plasma concentrations of total EPA and total DHA, and PK parameters over time under the three proposed conditions (fasting, before meal, and after meal). Analyses of the outcome measures presented are for baseline-adjusted data for total EPA and DHA since the presence of endogenous levels of these fatty acids would likely contribute to intra-subject variability and affect the analyses and interpretation. The geometric mean was calculated as the exponential of the arithmetic mean calculated from data on a log scale.

Outcome measures

Outcome measures
Measure	Fasting n=42 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered at the end of a 10-hour fast.	Before Meal n=42 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered before consumption of a low calorie, low-fat breakfast (within 30 minutes before starting food intake).	After Meal n=42 Participants Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered after consumption of a low calorie, low-fat breakfast (within 30 minutes after starting food intake).
The Effect of Food Timing (Fasting, Before Meal, and After Meal) on PK (AUC0-72) of AZD0585 in Healthy Male Japanese. Total EPA (n=42, 42, 42)	1.53 mg⋅h/mL Geometric Coefficient of Variation 76.1 • Interval 0.353 to 4.37	1.52 mg⋅h/mL Geometric Coefficient of Variation 112 • Interval 0.0682 to 4.95	2.76 mg⋅h/mL Geometric Coefficient of Variation 31.1 • Interval 0.912 to 5.04
The Effect of Food Timing (Fasting, Before Meal, and After Meal) on PK (AUC0-72) of AZD0585 in Healthy Male Japanese. Total DHA (n=42, 42, 42)	0.542 mg⋅h/mL Geometric Coefficient of Variation 80.4 • Interval 0.118 to 1.55	0.533 mg⋅h/mL Geometric Coefficient of Variation 66.0 • Interval 0.111 to 1.8	0.621 mg⋅h/mL Geometric Coefficient of Variation 75.8 • Interval 0.107 to 1.86

Adverse Events

Fasting

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Before Meal

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

After Meal

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fasting n=42 participants at risk Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered at the end of a 10-hour fast.	Before Meal n=42 participants at risk Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered before consumption of a low calorie, low-fat breakfast (within 30 minutes before starting food intake).	After Meal n=42 participants at risk Each subject received a single oral dose of 4 g AZD0585 on Day 1 of Visits 2, 3, and 4. Each dose was administered after consumption of a low calorie, low-fat breakfast (within 30 minutes after starting food intake).
Gastrointestinal disorders Diarrhoea	11.9% 5/42 • Number of events 5 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow up visit (Visit 5). Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of at least 10 days between each treatment visit.	14.3% 6/42 • Number of events 6 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow up visit (Visit 5). Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of at least 10 days between each treatment visit.	0.00% 0/42 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow up visit (Visit 5). Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of at least 10 days between each treatment visit.
Nervous system disorders Presyncope	0.00% 0/42 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow up visit (Visit 5). Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of at least 10 days between each treatment visit.	0.00% 0/42 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow up visit (Visit 5). Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of at least 10 days between each treatment visit.	2.4% 1/42 • Number of events 1 • All adverse events (AEs) were collected from randomisation (Visit 2, Day 1) until the follow up visit (Visit 5). Visits 2, 3 and 4 comprised 3 separate treatment periods with a washout period of at least 10 days between each treatment visit.

Additional Information

Stefan C Carlsson, MD, PhD, Global Clinical Lead

AstraZeneca Pharmaceuticals

Phone: +46 31 7761000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60