Essential Tremor
Conditions
Keywords
Ethanol, Alcohol Responsive, Movement Disorder, Gas Chromatography, Bioavailability, Pharmacokinetics, Essential Tremor
Brief summary
OVERVIEW Essential tremor (ET) is a common movement disorder affecting 0.4% of the general population and up to 14% of people 65 years and older. Response to medications such as beta blockers and primidone may be of benefit, but are often accompanied by intolerable side effects. Response to ethanol, on the other hand, has a roughly 80% chance of significant tremor reduction, though daily use of this as a treatment has potentially serious medical, social, and legal consequences. The leading hypothesis for ET pathophysiology is an unmasking of spontaneous oscillations originating in neurons of the inferior olive. Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of ET; however, 1-octanol does this at a dose much lower than that leading to intoxication, suggesting in may be useful in the treatment of essential tremor. Our initial studies with 1-octanol have shown it to be safe at dosages up to 64mg/kg without signs of intoxication, while at the same time showing benefit. OBJECTIVE We plan to evaluate the efficacy of different 1-octanol formulations in humans based on accelerometry and spirography. We will also evaluate drug and metabolite bioavailabilities using a high performance liquid chromatography (HPLC) detection method from plasma and urine samples. STUDY POPULATION We will study adult subjects with ethanol-responsive Essential Tremor (ET). DESIGN This study is designed as a two-phase unblinded inpatient study of adults with ET receiving weight-adjusted oral dosages of 2 different formulations of 1-octanol in a crossover fashion. Phase I of the study is designed to develop an octanol detection assay using HPLC. Four subjects will receive daily escalating dosages (1-32 mg/kg) of a single 1-octanol formulation followed by a crossover trial of both formulations at a dosage of 64 mg/kg. Phase II will study 20 subjects receiving one of the two formulations at 64 mg/kg on inpatient day 1 followed by a 24 hour period of close monitoring. The second formulation will be given on day 3 and the patient will again undergo close monitoring for 24 hours. OUTCOME MEASURES The primary outcome measures for the study will be efficacy based on tremor ratings from accelerometry and spirography. Secondary outcome measures will be the determination of bioavailability, pharmacodynamic and pharmacokinetic profiles of octanol #61864 and octanol #68751 and their metabolites.
Detailed description
OVERVIEW Essential tremor (ET) is a common movement disorder affecting 0.4% of the general population and up to 14% of people 65 years and older. Response to medications such as beta blockers and primidone may be of benefit, but are often accompanied by intolerable side effects. Response to ethanol, on the other hand, has a roughly 80% chance of significant tremor reduction, though daily use of this as a treatment has potentially serious medical, social, and legal consequences. The leading hypothesis for ET pathophysiology is an unmasking of spontaneous oscillations originating in neurons of the inferior olive. Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of ET; however, 1-octanol does this at a dose much lower than that leading to intoxication, suggesting it may be useful in the treatment of essential tremor. Our initial studies with 1-octanol have shown it to be safe at dosages up to 64mg/kg without signs of intoxication, while at the same time showing benefit. OBJECTIVE We plan to evaluate the efficacy of different 1-octanol formulations in humans based on accelerometry and spirography. We will also evaluate drug and metabolite bioavailabilities using a high performance liquid chromatography (HPLC) detection method from plasma and urine samples. STUDY POPULATION We will study adult subjects with ethanol-responsive Essential Tremor (ET). DESIGN This study is designed as a two-phase unblinded inpatient study of adults with ET receiving weight-adjusted oral dosages of 2 different formulations of 1-octanol in a crossover fashion. Phase I of the study is designed to develop an octanol detection assay using HPLC. Four subjects will receive daily escalating dosages (1-32 mg/kg) of a single 1-octanol formulation followed by a crossover trial of both formulations at a dosage of 64 mg/kg. Phase II will study 20 subjects receiving one of the two formulations at 64 mg/kg on inpatient day 1 followed by a 24 hour period of close monitoring. The second formulation will be given on day 3 and the patient will again undergo close monitoring for 24 hours. OUTCOME MEASURES The primary outcome measures for the study will be efficacy based on tremor ratings from accelerometry and spirography. Secondary outcome measures will be the determination of bioavailability, pharmacodynamic and pharmacokinetic profiles of octanol #61864 and octanol #68751 and their metabolites. Addendum: Based on the results of the assays for all subjects who participated in Part 1 and 2 of this protocol, we would like to conduct an exploratory study (Part 3) consisting of two subjects receiving a dose of 128mg/kg of 1-octanol. This is meant to primarily explore the plasma concentration of 1-octanol, while also providing valuable information regarding the safety and efficacy at this higher dose. The remainder of the experimental design will be maintained, with exception of additional safety precautions which will be discussed in the protocol and consent.
Interventions
DRUG1-Octanol
1-Octanol is an long-chain alcohol with potential therapeutic benefits in treating alcohol-responsive tremors based on unknown mechanisms. The intervention consisted of either 1) 1-octanol adsorbed to microcrystalline cellulose, NF (Avicel PH 102, FMC Corp., Philadelphia, PA), and fine particle silica (Sipernat 50S, Evonik Degussa Corp., Parsippany, NJ) and encapsulated in 50 mg and 250 mg dosages; or 2) a soft-gel capsule containing 1-octanol embedded in soybean oil at 50 mg and 800 mg dosages (Best Formulations Inc, City of Industry, CA).
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with alcohol-responsive Essential Tremor * Limb involvement should be a prominent feature of the Essential tremor * Patients must be willing and able to safely stop and remain off any medications used to treat essential tremor for at least 4 half-lives * Patients must be willing to abstain from ethanol and caffeine intake for at least 48 hours prior to starting the study hospitalization until study termination * Patients must be willing and able to fast for periods of up to 12 hours during the study
Exclusion criteria
* Patients with abnormalities other than tremor on neurological exam * Patients with active or past alcohol abuse or dependence * Patients with acute or chronic severe medical conditions such as renal failure, hepatic failure or lung disease * Patients taking primidone * Patients on other acute or chronic medications that influence hepatic metabolism or central nervous system (CNS) function and cannot be temporarily discontinued for the length of the study * Patients who do not wish to take a potentially intoxicating drug * Patients with abnormalities on their baseline screening laboratory tests * Women who are pregnant or lactating * Patients younger than age 21 * The presence of cognitive impairment preventing informed consent or cooperation during the study * People of Far East Asian or Native American descent, who may possess variant alleles of the genes for alcohol metabolism, i.e., alcohol dehydrogenase and aldehyde dehydrogenase, resulting in altered (slower) metabolism and potentially increased sensitivity to alcohols and their metabolites
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose | Spirography mean tremor amplitudes were measured in the right hand of each participant at 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose. Then, the scores of each participant were normalized (i.e., divided by) by their baseline tremor severity scores so that all scores are expressed as a proportion of the baseline score. Therefore, 1 is the baseline tremor severity, and lower scores indicate tremor reduction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose | Octanoic Acid is a metabolite of 1-octanol. Blood plasma levels of octanoic acid were measured at 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose. |
| Heart Rate Post 1-Octanol Dose | 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose | — |
| PR and QTc Intervals Post 1-Octanol Dose | 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Baseline is included for all participants who passed screening and received at least 1 dose of 1-octanol, whether in Part A, B or C | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A | Adverse Event | 1 | 0 |
| Part A | Screen failures | 6 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age Continuous | 68.1 years STANDARD_DEVIATION 8.1 |
| Age of onset | 39.5 years STANDARD_DEVIATION 18.6 |
| Body Mass Index | 28.6 kg/m^2 STANDARD_DEVIATION 4.7 |
| Disease Duration | 28.7 years STANDARD_DEVIATION 17.2 |
| Fahn Tolosa Marin Tremor Rating Scale | 41.6 scores on a scale STANDARD_DEVIATION 17.6 |
| Family history of essential tremor | 13 participants |
| Height | 169.6 centimeters STANDARD_DEVIATION 12 |
| History of alcohol-responsive tremors | 15 participants |
| Number of alcohol servings required for tremor response | 2.1 servings STANDARD_DEVIATION 0.3 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
| Weight | 82.9 kg STANDARD_DEVIATION 20.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 2 / 15 |
Outcome results
Primary
Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B
Spirography mean tremor amplitudes were measured in the right hand of each participant at 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose. Then, the scores of each participant were normalized (i.e., divided by) by their baseline tremor severity scores so that all scores are expressed as a proportion of the baseline score. Therefore, 1 is the baseline tremor severity, and lower scores indicate tremor reduction.
Time frame: 0, 15, 30, 60, 90, 120, 150, 180, 240 and 360 minutes post-dose
Population: All participants who received both formulations of 64 mg/kg 1-octanol in Part B
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 0 minutes | 1 normalized score on a scale | Standard Error 0 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 15 minutes post-dose | 1.009 normalized score on a scale | Standard Error 0.092 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 30 minutes post-dose | 0.826 normalized score on a scale | Standard Error 0.104 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 60 minutes post-dose | 0.786 normalized score on a scale | Standard Error 0.084 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 90 minutes post-dose | 0.670 normalized score on a scale | Standard Error 0.082 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 120 minutes post-dose | 0.662 normalized score on a scale | Standard Error 0.107 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 150 minutes post-dose | 0.680 normalized score on a scale | Standard Error 0.101 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 180 minutes post-dose | 0.645 normalized score on a scale | Standard Error 0.1 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 240 minutes post-dose | 0.791 normalized score on a scale | Standard Error 0.129 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 360 minutes post-dose | 0.894 normalized score on a scale | Standard Error 0.223 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 180 minutes post-dose | 0.707 normalized score on a scale | Standard Error 0.113 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 0 minutes | 1 normalized score on a scale | Standard Error 0 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 120 minutes post-dose | 0.709 normalized score on a scale | Standard Error 0.119 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 15 minutes post-dose | 0.901 normalized score on a scale | Standard Error 0.181 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 360 minutes post-dose | 0.122 normalized score on a scale | Standard Error 0.098 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 30 minutes post-dose | 0.738 normalized score on a scale | Standard Error 0.132 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 150 minutes post-dose | 0.746 normalized score on a scale | Standard Error 0.143 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 60 minutes post-dose | 0.766 normalized score on a scale | Standard Error 0.171 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 240 minutes post-dose | 0.683 normalized score on a scale | Standard Error 0.112 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Normalized Mean Tremor Amplitude for Both Formulations of 64 mg/kg 1-Octanol in Part B | Normalized score at 90 minutes post-dose | 0.685 normalized score on a scale | Standard Error 0.16 |
Secondary
Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose
Octanoic Acid is a metabolite of 1-octanol. Blood plasma levels of octanoic acid were measured at 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose.
Time frame: 5, 20, 45, 70, 100, 130, 160, 210, 270 and 360 minutes post-dose
Population: All participants who received either formulation 64 mg/kg 1-octanol in Part A or B
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 5 min post-dose | 62.94 ng/ml | Standard Deviation 29.37 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 20 min post-dose | 5064.12 ng/ml | Standard Deviation 4240.79 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 45 min post-dose | 7967.97 ng/ml | Standard Deviation 3078.81 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 70 min post-dose | 6788.58 ng/ml | Standard Deviation 2598.85 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 100 min post-dose | 5701.60 ng/ml | Standard Deviation 2207.62 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 130 min post-dose | 5448.23 ng/ml | Standard Deviation 1514.6 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 160 min post-dose | 4662.88 ng/ml | Standard Deviation 1719.1 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 210 min post-dose | 3179.10 ng/ml | Standard Deviation 1194.03 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 270 min post-dose | 2248.74 ng/ml | Standard Deviation 1192.6 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 360 min post-dose | 1266.37 ng/ml | Standard Deviation 822.56 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 210 min post-dose | 4307.74 ng/ml | Standard Deviation 3135.91 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 5 min post-dose | 74.16 ng/ml | Standard Deviation 38.78 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 130 min post-dose | 9605.68 ng/ml | Standard Deviation 3822.29 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 20 min post-dose | 3885.52 ng/ml | Standard Deviation 4111.65 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 360 min post-dose | 872.51 ng/ml | Standard Deviation 758.44 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 45 min post-dose | 9645.55 ng/ml | Standard Deviation 5805.79 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 160 min post-dose | 6678.69 ng/ml | Standard Deviation 2748.75 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 70 min post-dose | 13315.26 ng/ml | Standard Deviation 9162.85 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 270 min post-dose | 2618.25 ng/ml | Standard Deviation 2585.11 |
| 64 mg/kg 1-Octanol Soybean Oil Embedded (SOY) Formulation | Blood Plasma Levels of Octanoic Acid After 64 mg/kg 1-Octanol Dose | Plasma Octanoic Acid Level at 100 min post-dose | 9289.39 ng/ml | Standard Deviation 2998.95 |
Secondary
Heart Rate Post 1-Octanol Dose
Time frame: 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose
Population: All participants who received at least 1 dose of 1-octanol in Part A, B or C
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Heart Rate Post 1-Octanol Dose | Heart Rate at 0 min | 70.8 beats per minute | Standard Error 2.9 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Heart Rate Post 1-Octanol Dose | Heart Rate at 15 min | 66.6 beats per minute | Standard Error 2.7 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Heart Rate Post 1-Octanol Dose | Heart Rate at 100 min | 67.1 beats per minute | Standard Error 2.7 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | Heart Rate Post 1-Octanol Dose | Heart Rate at 24 hours | 72.4 beats per minute | Standard Error 2.7 |
Secondary
PR and QTc Intervals Post 1-Octanol Dose
Time frame: 0 minutes, 15 minutes, 100 minutes and 24 hours post-dose
Population: All participants who received at least 1 dose of 1-octanol in Part A, B or C
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | PR Interval at 0 min | 168.8 ms | Standard Error 6.6 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | PR Interval at 15 min | 172.8 ms | Standard Error 6.2 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | PR Interval at 100 min | 171.6 ms | Standard Error 6.2 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | PR Interval at 24 hours | 168.6 ms | Standard Error 6.2 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | QTc Interval at 0 min | 433.8 ms | Standard Error 8.4 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | QTc Interval at 15 min | 436.5 ms | Standard Error 7.4 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | QTc Interval at 100 min | 433.0 ms | Standard Error 7.4 |
| 64 mg/kg 1-Octanol Cellulose-based (CEL) Formulation | PR and QTc Intervals Post 1-Octanol Dose | QTc Interval at 24 hours | 437.4 ms | Standard Error 7.5 |