Safety, Tolerability, and Pharmacokinetic Study of Methylene Blue Following a 1 mg/kg Intravenous Dose in Healthy Adults

A One-Period, Single-Dose, Safety, Tolerability, and Pharmacokinetic Study of Methylene Blue Injection United States Pharmacopeia (USP) Following a 1 mg/kg Intravenous Dose in Healthy Adult Volunteers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02478281

Enrollment

Registered

2015-06-23

Start date

2012-10-31

Completion date

2013-03-31

Last updated

2025-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Methemoglobinemia, Methemoglobinemia

Brief summary

A Phase 1 trial to assess the single-dose safety, tolerability, and pharmacokinetic (PK) of Methylene Blue Injection, USP 1 mg/kg in healthy adult volunteers.

Detailed description

This is an open-label, single-center, one-arm, safety, tolerability, and PK study in healthy male and female volunteers of Methylene Blue Injection, USP. Following an overnight fast, twelve healthy adult male and female volunteers will receive a single dose of study drug at a dose of 1 mg/kg solution per kg given intravenously over a period of 5 minutes followed by serial venous blood sampling at 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 postdose.

Interventions

DRUGMethylene Blue

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

* Healthy adult male or female volunteers, 18-60 years of age, inclusive. * Weigh at least 52 kg for males and 45 kg for females and within the normal range according to accepted normal values of the Body Mass Index (BMI) chart 18.5-29.9 kg/m² inclusive. * Medically healthy with no clinically significant laboratory profiles, vital signs, or ECG's; as deemed by the PI. * For females of childbearing potential: either be sexually inactive (abstinent) for 14 days prior to the first dose and throughout the study or be using acceptable birth control methods. Female subjects who claim to be sexually inactive, but become sexually active during the course of the study must agree to use a barrier method (e.g. condom, diaphragm)with spermicide from the time of the start of sexual activity through at least 30 days following dosing. In addition, female subjects of childbearing potential will be advised to remain sexually inactive or to keep the same birth control method for at least 30 days following dosing. * Females of non-childbearing potential must have undergone one of the following sterilization procedures at least 6 months prior to Day 1: * Hysteroscopic tubal ligation (with a copy of the confirmation test) and be using a barrier method (condom or diaphragm) and spermicide throughout the study; * Bilateral tubal ligation and be using a barrier method (condom or diaphragm) and spermicide throughout the study; * Hysterectomy; * Bilateral oophorectomy or be postmenopausal with amenorrhea for at least 1 year prior to Day 1 and follicle stimulating hormone (FSH) serum levels ≥ 40 milli-International Units per mL (mIU/mL). Females on hormone replacement therapy may be deemed eligible for participation in the study even if their FSH levels \< 40 mIU/mL, if they are able to provide documentation of FSH levels 40 mIU/mL before initiation of hormone replacement therapy. * Males must use condom with spermicide when engaged in sexual activity and must agree to refrain from sperm donation from check-in through 90 days postdose. * Willing to answer inclusion and

Exclusion criteria

questionnaire at check-in. * Give voluntary written informed consent to participate in the study. * Be able to comply with the protocol and the assessments therein.

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC 0-t)	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	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
Area Under the Curve From Time Zero Extrapolated to Infinity (AUC 0-∞)	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	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.
The Percent of Extrapolated Area Under the Curve (AUC%Extrap)	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	The AUC%extrap refers to the fraction of the total AUC that is due to the extrapolated AUC
Area Under the Curve Ratio (AUCR)	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	AUCR refers to the ratio of AUC 0-t to AUC 0-∞.
Total Body Clearance (CL)	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	CL refers to the Dose/AUC 0-∞
Maximum Measured Plasma Concentration (Cmax)	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	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.
Time to Maximum Plasma Concentration (Tmax)	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	Tmax refers to the time it takes for a drug to reach maximum concentration
Terminal Elimination Half-life (T1/2)	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	T1/2 refers to the time taken for concentration of a drug to decrease from its maximum concentration to half of Cmax
Terminal Elimination Rate Constant (Lambda Z)	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	Lambda Z refers to the terminal elimination phase for drug plasma concentration vs. time data
Volume of Distribution (Vz) Based on Terminal Phase	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	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.
Mean Residence Time (MRT)	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	MRT refers to the average amount of time that a drug molecule spends in the body before being removed

Participant flow

Recruitment details

Participants were recruited at 1 investigator center.

Pre-assignment details

Of the 12 participants enrolled, all met eligibility requirements and were treated.

Participants by arm

Arm	Count
Methylene Blue Injection, USP 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	12
Total	12

Baseline characteristics

Characteristic	Methylene Blue Injection, USP
Age, Continuous	35.3 years STANDARD_DEVIATION 9.84
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	5 Participants
Race (NIH/OMB) More than one race	0 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	7 Participants
Region of Enrollment United States	12 Participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	7 Participants
Weight	76.13 kilograms STANDARD_DEVIATION 11.75

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 12
other Total, other adverse events	10 / 12
serious Total, serious adverse events	0 / 12

Outcome results

Primary

Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC 0-t)

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