Growth and Development
Conditions
Brief summary
This study is designed to compare the incremental area under the curve from 0 to 24h (iAUC0-24h) of plasma levels of n-3 fatty acids (sum of total and free eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) after ingestion of an emulsified product and a non-emulsified reference control of free flowing cod liver oil at the lowest appropriate dose that is practically acceptable, and as near as possible to the test products' recommended daily dose.
Detailed description
Many dietary lipids are in the form of triglycerides, ethyl esters or phospholipids. During digestion these lipids are subject to hydrolysis, in particular by pancreatic triglyceride lipase. To facilitate the action of the enzyme, lipids are emulsified by the action of bile salts. By increasing the surface area of the fat globules, emulsification increases access to the lipids by pancreatic triglyceride lipase. This study is designed to compare iAUC0-24h of plasma levels of n-3 fatty acids (sum of total and free EPA and DHA) after ingestion of an emulsified product and a non-emulsified reference control of free flowing cod liver oil at the lowest appropriate dose that is practically acceptable, and as near as possible to the test products' recommended daily dose.
Interventions
OTHEREmulsified cod liver oil product
Participants are required to consume the dose (30 mL) within 1 min, followed by up to 300 mL of apple juice which needs to be consumed within 2 min
OTHERNon-emulsified cod liver oil product
Participants are required to consume the dose (5.8 mL) within 1 min, followed by up to 300 mL of apple juice which needs to be consumed within 2 min
Sponsors
Hammersmith Medicines Research
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers aged 18 to 45 years (both inclusive) * Body mass index (BMI) of 18.5-29.9 kg/m2 inclusive
Exclusion criteria
* Pregnant or lactating women * Allergy/intolerance to any study material * Current or recurrent disease, within 12 months of screening that could affect the metabolism of drug * Participants who have taken any drug known to induce or inhibit hepatic drug metabolism in 30 days prior to screening * Positive serum Hepatitis B surface antigen, Hepatitis C antibodies or Human Immunodeficiency Virus (HIV), alcohol or drug abuse * Smokers taking \>5 cigarettes/day; prior or current use of any other nicotine containing product * Blood donated within 3 months of screening * Consumed n-3 rich food or beverage or n-3 fortified food or beverage within 72h prior to each study session
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incremental Area Under the Curve to 24 Hours (h) (iAUC0-24h) of the Sum of Plasma Total and Free n-3 Fatty Acids (Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) | Baseline and up to Day 2 | The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, 10, 12 and 24 h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| iAUC0-24h of Sum of Total and Free EPA | Baseline and up to Day 2 | The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, 10, 12 and 24 h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values. |
| iAUC0-10h of Sum of Total and Free DHA | Upto 10 h | The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, and 10h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values. |
| iAUC0-10h of Sum of Total and Free EPA | Upto 10 h | The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, and 10h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values. |
| iAUC0-10h of Sum of Total and Free DHA and EPA | Upto 10 h | The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, and 10h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values. |
| Maximum Concentration (Cmax) of Sum of Total and Free DHA and EPA | Baseline and up to Day 2 | Blood sampleswere taken at time points 0,2,4,6,8,10,12 and 24h. Maximum plasma concentration was determined. |
| iAUC0-24h of Sum of Total and Free DHA | Baseline and up to Day 2 | The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, 10, 12 and 24 h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values. |
| Cmax of Sum of Total and Free EPA | Baseline and up to Day 2 | Blood sampleswere taken at time points 0,2,4,6,8,10,12 and 24h. Maximum plasma concentration was determined. |
| Time to Maximum Concentration (Tmax) of Sum of Total and Free DHA and EPA | Baseline and up to Day 2 | Blood samples will be taken at time points 0,2,4,6,8,10,12 and 24h. Time to maximum concentration was determined. |
| Tmax of Sum of Total and Free DHA | Baseline and up to Day 2 | Blood samples will be taken at time points 0,2,4,6,8,10,12 and 24h. Time to maximum concentration was determined. |
| Tmax of Sum of Total and Free EPA | Baseline and up to Day 2 | Blood samples will be taken at time points 0,2,4,6,8,10,12 and 24h.Time to maximum concentration was determined. |
| Cmax of Sum of Total and Free DHA | Baseline and up to Day 2 | Blood samples were taken at time points 0,2,4,6,8,10,12 and 24h. Maximum plasma concentration was determined. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were recruited at one Centre in United Kingdom.
Pre-assignment details
A total of 93 participants were screened, out of which 50 participants were randomized. 39 participants failed screening and 2 participants withdrew from the study. 2 participants discontinued due to other reasons (reason not specified).
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Test product : 30 mL Scott's Emulsion containing 10% Cod Liver Oil, 10% Cod Oil. Reference product: 5.8 mL of non emulsified free flowing cod liver oil | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period 1 | Screen Failure | 1 | 2 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 29.1 Years STANDARD_DEVIATION 7.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 49 |
| other Total, other adverse events | 9 / 48 | 3 / 49 |
| serious Total, serious adverse events | 0 / 48 | 0 / 49 |
Outcome results
Primary
Incremental Area Under the Curve to 24 Hours (h) (iAUC0-24h) of the Sum of Plasma Total and Free n-3 Fatty Acids (Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA)
The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, 10, 12 and 24 h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values.
Time frame: Baseline and up to Day 2
Population: Per protocol (PP) population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Incremental Area Under the Curve to 24 Hours (h) (iAUC0-24h) of the Sum of Plasma Total and Free n-3 Fatty Acids (Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) | 13.19 Microgram per mililiter (µg/mL) | Standard Deviation 8.368 |
| Reference Product | Incremental Area Under the Curve to 24 Hours (h) (iAUC0-24h) of the Sum of Plasma Total and Free n-3 Fatty Acids (Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA) | 7.73 Microgram per mililiter (µg/mL) | Standard Deviation 6.532 |
p-value: <0.000195% CI: [2.79, 7.53]ANCOVA
Secondary
Cmax of Sum of Total and Free DHA
Blood samples were taken at time points 0,2,4,6,8,10,12 and 24h. Maximum plasma concentration was determined.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmax of Sum of Total and Free DHA | 70.61 µg/mL | Standard Deviation 19.698 |
| Reference Product | Cmax of Sum of Total and Free DHA | 64.73 µg/mL | Standard Deviation 19.229 |
Secondary
Cmax of Sum of Total and Free EPA
Blood sampleswere taken at time points 0,2,4,6,8,10,12 and 24h. Maximum plasma concentration was determined.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Cmax of Sum of Total and Free EPA | 28.89 µg/mL | Standard Deviation 8.205 |
| Reference Product | Cmax of Sum of Total and Free EPA | 26.27 µg/mL | Standard Deviation 8.894 |
Secondary
iAUC0-10h of Sum of Total and Free DHA
The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, and 10h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values.
Time frame: Upto 10 h
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | iAUC0-10h of Sum of Total and Free DHA | 7.51 µg/mL | Standard Deviation 6.81 |
| Reference Product | iAUC0-10h of Sum of Total and Free DHA | 3.86 µg/mL | Standard Deviation 4.011 |
Secondary
iAUC0-10h of Sum of Total and Free DHA and EPA
The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, and 10h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values.
Time frame: Upto 10 h
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | iAUC0-10h of Sum of Total and Free DHA and EPA | 14.79 µg/mL | Standard Deviation 9.336 |
| Reference Product | iAUC0-10h of Sum of Total and Free DHA and EPA | 7.83 µg/mL | Standard Deviation 6.133 |
Secondary
iAUC0-10h of Sum of Total and Free EPA
The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, and 10h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values.
Time frame: Upto 10 h
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | iAUC0-10h of Sum of Total and Free EPA | 7.28 µg/mL | Standard Deviation 2.893 |
| Reference Product | iAUC0-10h of Sum of Total and Free EPA | 3.97 µg/mL | Standard Deviation 2.493 |
Secondary
iAUC0-24h of Sum of Total and Free DHA
The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, 10, 12 and 24 h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | iAUC0-24h of Sum of Total and Free DHA | 5.09 µg/mL | Standard Deviation 6.118 |
| Reference Product | iAUC0-24h of Sum of Total and Free DHA | 2.89 µg/mL | Standard Deviation 4.225 |
Secondary
iAUC0-24h of Sum of Total and Free EPA
The AUC was calculated using the trapezoidal method and using nominal time points from 0, 2, 4, 6, 8, 10, 12 and 24 h respectively. The AUC was divided by the total duration to represent a weighted mean incremental change over time. Higher values of AUC demonstrate better rate of absorption over time than lower values.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | iAUC0-24h of Sum of Total and Free EPA | 8.10 µg/mL | Standard Deviation 2.81 |
| Reference Product | iAUC0-24h of Sum of Total and Free EPA | 4.84 µg/mL | Standard Deviation 2.903 |
Secondary
Maximum Concentration (Cmax) of Sum of Total and Free DHA and EPA
Blood sampleswere taken at time points 0,2,4,6,8,10,12 and 24h. Maximum plasma concentration was determined.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Maximum Concentration (Cmax) of Sum of Total and Free DHA and EPA | 98.37 µg/mL | Standard Deviation 26.595 |
| Reference Product | Maximum Concentration (Cmax) of Sum of Total and Free DHA and EPA | 90.48 µg/mL | Standard Deviation 26.252 |
Secondary
Time to Maximum Concentration (Tmax) of Sum of Total and Free DHA and EPA
Blood samples will be taken at time points 0,2,4,6,8,10,12 and 24h. Time to maximum concentration was determined.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Time to Maximum Concentration (Tmax) of Sum of Total and Free DHA and EPA | 5.77 h | Standard Deviation 2.208 |
| Reference Product | Time to Maximum Concentration (Tmax) of Sum of Total and Free DHA and EPA | 7.73 h | Standard Deviation 3.48 |
Secondary
Tmax of Sum of Total and Free DHA
Blood samples will be taken at time points 0,2,4,6,8,10,12 and 24h. Time to maximum concentration was determined.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Tmax of Sum of Total and Free DHA | 5.23 h | Standard Deviation 1.79 |
| Reference Product | Tmax of Sum of Total and Free DHA | 7.56 h | Standard Deviation 4.219 |
Secondary
Tmax of Sum of Total and Free EPA
Blood samples will be taken at time points 0,2,4,6,8,10,12 and 24h.Time to maximum concentration was determined.
Time frame: Baseline and up to Day 2
Population: PP population (N=47) was the primary population of analysis defined as all participants in the safety population who have at least one post-baseline assessment of efficacy considered unaffected by protocol violations. From the PP population, 3 participants were not analysed in test group and 2 in control group, due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product | Tmax of Sum of Total and Free EPA | 8.36 h | Standard Deviation 4.979 |
| Reference Product | Tmax of Sum of Total and Free EPA | 8.00 h | Standard Deviation 3.464 |