Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetic Study of Methylene Blue Following a 1 mg/kg Intravenous Dose in Healthy Adults (NCT NCT02478281)
NCT ID: NCT02478281
Last Updated: 2025-06-05
Results Overview
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUC 0-t is defined as AUC from time 0 to the last data point
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
12 participants
Primary outcome timeframe
pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dose
Results posted on
2025-06-05
Participant Flow
Participants were recruited at 1 investigator center.
Of the 12 participants enrolled, all met eligibility requirements and were treated.
Participant milestones
| Measure |
Methylene Blue Injection, USP
Single dose of Methylene Blue Injection, United States Pharmacopeia (USP) at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability, and Pharmacokinetic Study of Methylene Blue Following a 1 mg/kg Intravenous Dose in Healthy Adults
Baseline characteristics by cohort
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Age, Continuous
|
35.3 years
STANDARD_DEVIATION 9.84 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 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
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 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
|
|
Region of Enrollment
United States
|
12 Participants
n=5 Participants
|
|
Weight
|
76.13 kilograms
STANDARD_DEVIATION 11.75 • n=5 Participants
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUC 0-t is defined as AUC from time 0 to the last data point
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC 0-t)
|
2600.09 ng*hr/mL
Geometric Coefficient of Variation 28.7
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC 0-∞ is defined as area under the concentration vs. time curve from zero to infinity.
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Area Under the Curve From Time Zero Extrapolated to Infinity (AUC 0-∞)
|
2967.09 ng*hr/mL
Geometric Coefficient of Variation 27.9
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
The AUC%extrap refers to the fraction of the total AUC that is due to the extrapolated AUC
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
The Percent of Extrapolated Area Under the Curve (AUC%Extrap)
|
11.72 Percent of AUC
Geometric Coefficient of Variation 32.9
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
AUCR refers to the ratio of AUC 0-t to AUC 0-∞.
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Area Under the Curve Ratio (AUCR)
|
87.63 Percent
Geometric Coefficient of Variation 4.6
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
CL refers to the Dose/AUC 0-∞
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Total Body Clearance (CL)
|
19.02 L/hour
Geometric Coefficient of Variation 22.5
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to Treat
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Maximum Measured Plasma Concentration (Cmax)
|
457.34 ng/mL
Geometric Coefficient of Variation 41.9
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to Treat
Tmax refers to the time it takes for a drug to reach maximum concentration
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Time to Maximum Plasma Concentration (Tmax)
|
0.217 Hours
Geometric Coefficient of Variation 126.7
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to Treat
T1/2 refers to the time taken for concentration of a drug to decrease from its maximum concentration to half of Cmax
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Terminal Elimination Half-life (T1/2)
|
15.908 Hours
Geometric Coefficient of Variation 46.3
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to Treat
Lambda Z refers to the terminal elimination phase for drug plasma concentration vs. time data
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Terminal Elimination Rate Constant (Lambda Z)
|
0.04357 1/hour
Geometric Coefficient of Variation 46.3
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
Vz refers to the ratio of amount of drug in a body (dose) to concentration of the drug that is measured in blood, plasma, and un-bound in interstitial fluid.
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Volume of Distribution (Vz) Based on Terminal Phase
|
436.557 Liters
Geometric Coefficient of Variation 40.3
|
PRIMARY outcome
Timeframe: pre-dose, 0.042, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 16, 36, 48, and 72 hours post-dosePopulation: Intent to treat
MRT refers to the average amount of time that a drug molecule spends in the body before being removed
Outcome measures
| Measure |
Methylene Blue Injection, USP
n=12 Participants
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Mean Residence Time (MRT)
|
17.677 Hours
Geometric Coefficient of Variation 39.8
|
Adverse Events
Methylene Blue Injection, USP
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Methylene Blue Injection, USP
n=12 participants at risk
Single dose of Methylene Blue Injection, USP at a dose of 1 mg/kg solution per kg given intravenously over a period of approximately 5 minutes.
Methylene Blue
|
|---|---|
|
Cardiac disorders
Tachycardia
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Gastrointestinal disorders
Diarrhea
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Gastrointestinal disorders
Dyspepsia
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Gastrointestinal disorders
Nausea
|
16.7%
2/12 • Number of events 2 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
General disorders
Feeling hot
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
General disorders
Infusion site extravasation
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
General disorders
Infusion site pain
|
41.7%
5/12 • Number of events 5 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
General disorders
Infusion site pruritus
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
General disorders
Vessel puncture site hematoma
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Investigations
Alanine aminotransferase increased
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 1 • 4 days
An adverse event was defined as any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place