MethemoglobinemiaPhase 1NCT02478281

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

A Phase 1 study testing Methylene Blue in people with Methemoglobinemia and Congenital Methemoglobinemia, run by American Regent, Inc..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Methemoglobinemia, Congenital Methemoglobinemia
What is being tested?: Methylene Blue
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: No sites listed yet
Study dates: Oct 2012to Mar 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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;

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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.

Who cannot join

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease in the opinion of the PI.
History or presence of alcoholism within the past 2 years.
History or presence of drug abuse within the past 2 years.
History or presence of hypersensitivity or idiosyncratic reaction to Methylene Blue.
History or presence of Glucose-6-Phosphate Dehydrogenase (G6PD) dehydrogenase deficiency, retinopathy, blood disorder, myasthenia gravis, psoriasis, epilepsy, clinically significant allergies (except for mild forms of hay fever), or any other clinically significant medical condition, which in the opinion of the PI, might interfere with study participation.
History or laboratory evidence of renal insufficiency.

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Any screening laboratory test with clinically significant abnormalities in the opinion of the PI (including cell blood count, creatinine, or liver function tests).
Have used any drug that acts as a serotonin reuptake inhibitor (SRIs) e.g. selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, or ergot alkaloids within 30 days (or 5 half-lives of the compound, whichever is longer) prior to study drug dosing.
Female subjects who are pregnant or lactating, or female subjects who are likely to become pregnant during the study.
Had positive results for the urine drug/alcohol screen at screening or check-in.
Had positive results at screening for HIV, HBsAg, or hepatitis C virus (HCV).
Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.
Heart rate is lower than 40 bpm or higher than 99 bpm at screening.
QTc interval is >430 msec (males) or >450 msec (females) or deemed clinically abnormal by the PI or use of any drug or agent suspected of causing QT prolongation or torsade de pointes within 14 days (or 5 half- lives of the compound, whichever is longer) prior to study drug dosing.
Have been on a special diet (for whatever reason) within the 28 days prior to study drug dosing, and throughout the study.
Have made a donation of blood or had significant blood loss within 56 days prior to study drug dosing.
Have made a plasma donation within 7 days prior to study drug dosing.
Have received Methylene Blue within 72 hours prior to study drug dosing.
Have participated in another clinical trial within 30 days (or 5 half-lives of the compound, whichever is longer) prior to study drug dosing.

About this study

Official title: 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

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.

Read the 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.

Conditions: Methemoglobinemia, Congenital Methemoglobinemia
Being tested: Methylene Blue
Medical subject headings: Methemoglobinemia, Congenital Methemoglobinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Methylene BlueDrug

Study groups in NCT02478281
Study group	Role	What they receive
Methylene Blue Injection, United States Pharmacopeia (USP)	Experimental	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. Receives: Drug: Methylene Blue

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2012Mar 2013

First posted23 Jun 2015 (estimated)
Study startOct 2012
Primary completionOct 2012
Study completionMar 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for MethemoglobinemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02478281
Sponsor's protocol ID: 1MBL12002
Status last verified: Jan 2018
First submitted: 28 Apr 2015
Last updated: 5 Jun 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 5 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT02478281
Acronym / sponsor ID: 1MBL12002
Conditions: Methemoglobinemia, Congenital Methemoglobinemia
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: American Regent, Inc.Industry (pharma, biotech, devices)
Study start: Oct 2012
Primary completion: Oct 2012 (actual)
Study completion: Mar 2013 (actual)
First posted: 23 Jun 2015 (estimated)
Results: Posted 5 Jun 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Methylene Blue Injection, United States Pharmacopeia (USP)	Experimental	Drug: Methylene BlueSingle 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.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (13 listed)

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:

Key exclusion criteria (19 listed)

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease in the opinion of the PI.
History or presence of alcoholism within the past 2 years.
History or presence of drug abuse within the past 2 years.
History or presence of hypersensitivity or idiosyncratic reaction to Methylene Blue.
History or presence of Glucose-6-Phosphate Dehydrogenase (G6PD) dehydrogenase deficiency, retinopathy, blood disorder, myasthenia gravis, psoriasis, epilepsy, clinically significant allergies (except for mild forms of hay fever), or any other clinically significant medical condition, which in the opinion of the PI, might interfere with study participation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Methylene Blue	Drug	Methylene Blue Injection, United States Pharmacopeia (USP)

Primary outcome

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

Results and safety

Results posted to the registry on 5 Jun 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Methylene Blue Injection, USP	12	12

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

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Methylene Blue Injection, USP n = 12
Value	2600.09 (28.7)

Population analysed: Intent to treat

Primary outcome: Area Under the Curve From Time Zero Extrapolated to Infinity (AUC 0-∞)

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Methylene Blue Injection, USP n = 12
Value	2967.09 (27.9)

Population analysed: Intent to treat

Primary outcome: The Percent of Extrapolated Area Under the Curve (AUC%Extrap)

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: Percent of AUC

Measure	Methylene Blue Injection, USP n = 12
Value	11.72 (32.9)

Population analysed: Intent to treat

Primary outcome: Area Under the Curve Ratio (AUCR)

Time frame: 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. Geometric mean (Geometric Coefficient of Variation). Unit: Percent

Measure	Methylene Blue Injection, USP n = 12
Value	87.63 (4.6)

Population analysed: Intent to treat

Adverse events

Time frame: 4 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Methylene Blue Injection, USP	0 of 12 (0%)	10 of 12 (83.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Fareeda Hosein, MD principal investigator

Celerion

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Methylene Blue in people with Methemoglobinemia and Congenital Methemoglobinemia, run by American Regent, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC 0-t) (time frame: 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 study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02478281.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2025.