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The main purpose of this study is to determine the safety, feasibility, and utility of intranasal (NAS) ketamine in persistent uncontrolled cancer related pain. In this prospective clinical trial the researchers will investigate the use of NAS ketamine in patients with pain related to cancer or cancer treatment. The researchers plan to enroll at least 25 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the supportive oncology clinic, oncology clinics, the pain clinic and Acute Pain Service at Emory. Participants will be asked to return to the Phase I unit of the Winship Cancer Building C for a total of 5 study visits, each two to five days apart. During these visits participants will complete questionnaires, have blood samples drawn and will have study medication administered to them in escalating doses. For safety monitoring participants will be contacted by telephone 14 days after the last dose of medication administered.
There are about 11.9 million Americans affected with cancer. 53% of patients with cancer experience pain at all stages of cancer. These patients often require high doses of opioids with uncontrolled pain that makes them too sedated to effectively participate in day-to-day activities and have a good quality of life. Depression often co-exists with cancer pain due to the nature of the disease. The researchers are searching for improved therapies for chronic cancer pain and ketamine with its novel mechanism of action may be a promising solution.
Ketamine is an FDA approved anesthetic with the ability to effect memory loss, pain relief and sedation. Safety and efficacy of ketamine as an anesthetic and analgesic agent is well documented. Low doses of ketamine have minimal adverse impact on circulatory or breathing functions but can reduce pain. Research has shown that ketamine is effective in controlling breakthrough pain and reducing depression in a randomized double blind controlled trial. There is limited data regarding the use of ketamine for pain management in cancer.
One of the challenges with ketamine is the route of administration, most commonly given intravenously (IV) or intramuscularly (IM). It has also been given by mouth and rectally, but absorption is very poor. Intranasal (NAS) administration may be a promising method of delivery and can be ordered by a physician from a compounding pharmacy. From other research the investigators expect absorption to be higher than oral or rectal administration and this method of delivery as needle-free is a patient-friendly route of administration.
The main purpose of this study is to determine the safety, feasibility, and utility of intranasal (NAS) ketamine in persistent uncontrolled cancer related pain. In this prospective clinical trial the researchers will investigate the use of NAS ketamine in patients with pain related to cancer or cancer treatment. The researchers plan to enroll at least 15 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the oncology clinic, pain clinic and Acute Pain Service at Emory. Participants will be asked to return to the Phase I unit of the Winship Cancer Building C for a total of 5 study visits, each two to five days apart. During these visits participants will complete questionnaires, have blood samples drawn and will have study medication administered to them in escalating doses. For safety monitoring participants will be contacted by telephone 14 days after the last dose of medication administered.
Data obtained from this study will help determine if ketamine provides a reduction of pain using the Numeric Pain Rating Scale and a reduction in the use of opioid consumption and other rescue medications. Additionally the researchers will study the bioavailability, pharmacodynamics and pharmacokinetics of ketamine and the safety profile of NAS ketamine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intranasal ketamine treatment | Experimental | Study participants who are receiving intranasal ketamine treatments. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intranasal ketamine | Drug | 10mg of intranasal ketamine will be given to make sure that the study patients are able to tolerate a small dose of NAS ketamine. On the second visit, 10 mg of IV ketamine will be given to help establish bioavailability of NAS ketamine, with patients serving as their own controls. On the third and fourth visit, higher doses of ketamine, 30 mg and 50 mg respectively, will be given. All doses of ketamine will be administered by an anesthesia research nurse. |
| Measure | Description | Time Frame |
|---|---|---|
| Bioavailability of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the bioavailability (a pharmacokinetic characteristic) of intranasal and intravenous ketamine. Bioavailability is assessed as nanograms per milliliter (ng/mL) of ketamine circulating in blood. Each study participant received each dose of ketamine during separate study visits. Samples were obtained prior to ketamine administration, and at 2, 30, 60 and 240 minutes after medication administration, during study visits 1 through 4. The baseline sample was not collected at the first study visit as assessing prior intake of ketamine was not necessary. | Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks |
| Peak Concentration (Cmax) of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the peak concentration (Cmax) of intranasal and intravenous ketamine. Peak concentration is assessed as the maximum ng/mL of ketamine circulating in blood. Each study participant received each dose of ketamine during separate study visits. Samples were obtained at 2, 30, 60 and 240 minutes after medication administration. | Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks |
| Area Under the Curve of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the elimination (a pharmacokinetic characteristic) of intranasal and intravenous ketamine. Elimination of the drug disappearing from the body is assessed as the area under the curve (AUC). Each study participant received each dose of ketamine during separate study visits. Samples were obtained at 2, 30, 60 and 240 minutes after medication administration. Each subject did not have quantitative levels at all time points. There were not enough data to construct a curve for each participant and therefore calculate an AUC. Data from all participants were naively pooled to calculate one AUC for the entire population (i.e., across all participants' data). | Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Rescue Medication Use | The opioid sparing effect of NAS ketamine will be determined by evaluating frequency of rescue medications use prior to and during the study. | Visit 1 through Visit 5, up to 6 weeks |
| Total Opioid Consumption |
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Inclusion Criteria:
Patients with uncontrolled pain related to cancer or cancer treatment. Uncontrolled pain will be defined as:
Patients who are able to follow-up in person during the trial
Patient on stable analgesic regimen for >7 days without escalation during study period with rescue or immediate release medication every 3 hours or longer
Patients who are willing and able to maintain a daily pain diary
Patients who are able to understand written and verbal English
Patient weight >/= 50 kg
Exclusion Criteria:
Transportation issues interfering with return study visits
Patients with high disposition of laryngospasm or apnea
Presence of severe cardiac disease
Presence of conditions where significant elevations in blood pressure would be a serious hazard.
Stage 2 hypertension or greater (systolic blood pressure > 160 and/or diastolic blood pressure >100)
Baseline tachycardia, heart rate (HR) >100
History of seizures, elevated intracranial pressure (ICP) or cerebrospinal fluid (CSF) obstructive states (e.g. severe head injury, central congenital or mass lesions)
Conditions that may increase intraocular pressure (e.g. glaucoma, acute globe injury)
History of uncontrolled depression or other psychiatric comorbidity with psychosis
History of liver disease
History of interstitial cystitis
History of nasal or sinus anomalies or dysfunction e.g. allergic or infectious rhinitis.
Patients with lesions to the nasal mucosa
Pregnant women, nursing mothers and women of childbearing potential not using contraception known to be highly effective. Highly effective contraception methods include combination of any two of the following:
Illicit substance abuse within the past 6 months
Documented history of medication abuse/misuse (e.g. Unsanctioned dose escalation, broken opioid agreement etc.)
Clinical requirement for medications that are concurrent inducers or inhibitors of CYP3A4. CYP3A4 substrates are allowed.
Porphyria (possibility of triggering a porphyric reaction)
Severe active anemia ( a hemoglobin< 8 documented by labs drawn within 3 months of first study treatment)
History of difficult intravenous access
Intractable vomiting
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| Name | Affiliation | Role |
|---|---|---|
| Vinita Singh, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Winship Cancer Institute | Atlanta | Georgia | 30322 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31038469 | Background | Shteamer JW, Harvey RD, Spektor B, Curseen K, Egan K, Chen Z, Gillespie TW, Sniecinski RM, Singh V. Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial. JMIR Res Protoc. 2019 Apr 30;8(4):e12125. doi: 10.2196/12125. |
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Participants will be recruited from the supportive oncology clinic, oncology clinics, and pain clinics at Emory University in Atlanta, Georgia. Participant enrollment began July 25, 2017 and all follow up was complete by April 22, 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine Treatment | On the first study visit, 10mg of intranasal ketamine was given to make sure that the study patients could tolerate a small dose of intranasal ketamine. On the second visit, 10 mg of intravenous (IV) ketamine was given to compare the two routes of ketamine administration, with patients serving as their own controls. On the third and fourth visit, higher doses of intranasal ketamine, 30 mg and 50 mg respectively, were given, if the patients did not have severe adverse events with the smaller dosage. Participants returned for a fifth visit, 24 hours after Visit 4, to provide a blood sample and complete questionnaires. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intranasal Ketamine Treatment | Study participants receiving three different doses of intranasal ketamine and one dose of IV ketamine, at four different study visits, for treatment of cancer pain. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Bioavailability of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the bioavailability (a pharmacokinetic characteristic) of intranasal and intravenous ketamine. Bioavailability is assessed as nanograms per milliliter (ng/mL) of ketamine circulating in blood. Each study participant received each dose of ketamine during separate study visits. Samples were obtained prior to ketamine administration, and at 2, 30, 60 and 240 minutes after medication administration, during study visits 1 through 4. The baseline sample was not collected at the first study visit as assessing prior intake of ketamine was not necessary. | The baseline measurement was not collected during the visit where 10 mg of intranasal ketamine was administered. This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome. | Posted | Geometric Mean | Standard Deviation | ng/mL | Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks |
|
Data collection for adverse events began at the first study visit and were followed by a telephone call 14 days after the last dose of study medication administration, up to 6 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 10 mg Intranasal Ketamine | Study participants receiving 10 mg of intranasal ketamine. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Agitation | Psychiatric disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vinita Singh, MD | Emory University | 404-686-2410 | vinita.singh@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 1, 2019 | Apr 21, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D010146 | Pain |
| D000072716 | Cancer Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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|
| Time to Peak Concentration (Tmax) of Ketamine |
Blood samples were obtained at the study visits where ketamine was administered to measure the time to peak concentration (Tmax) of intranasal and intravenous ketamine. Time is measured as minutes after administration when the maximum concentration of ketamine in blood is reached. |
| Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks |
| Numerical Pain Rating Scale (NPRS) Score | The Numerical Pain Rating Scale (NPRS) was used to evaluate patient reported pain. Pain scores were recorded prior to and at 5,10,15, 30, 45, 60, 120, 180 and 240 minutes after administration of ketamine. The NPRS asks participants rate their current level of pain intensity on a scale from 0 (no pain) to 10 (worst possible pain). In general, improvements of pain severity of 1.5 points or less on NPRS could be seen as clinically irrelevant. Above that value, the cutoff point for "clinical relevance" depends on patients' baseline pain severity, and ranges from 2.4 to 5.3. Higher baseline scores require larger raw changes to represent clinically important differences. | Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score | To evaluate self-reported fatigue, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score | To evaluate self-reported dizziness, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score | To evaluate self-reported nausea, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score | To evaluate self-reported headache, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score | To evaluate self-reported feeling of unreality, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score | To evaluate self-reported change in hearing, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score | To evaluate self-reported change in vision, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score | To evaluate self-reported mood change, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score | To evaluate self-reported general discomfort, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score | To evaluate self-reported hallucinations, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
| Montgomery Asberg Depression Rating Scale (MADRS) Score | Depression was assessed on the Montgomery Asberg Depression Rating Scale (MADRS) during each study visit, before medication administration and 180 minutes after medication administration. The MADRS is designed to be particularly sensitive to treatment effects. The MADRS is a 10-item scale where the survey administrator rates the participant on a variety of aspects related to depression (such as apparent sadness, tension, and pessimistic thoughts) based on a clinical interview. Responses are provided on a scale of 0 to 6 where 0 signifies no difficulties in this area and 6 signifies severe difficulty. Total scores range from 0 to 60 with higher scores indicating greater severity of depression. | Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks |
| Edmonton Symptom Assessment System (ESAS) Score | The Edmonton Symptom Assessment System (ESAS) assesses nine symptoms that are common in cancer patients: pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and well-being. Each symptom is rated on a scale ranging from 0 (absence of symptom) to 10 (worst possible degree of symptom). The ESAS was administered at the baseline time point at each study visit. | Baseline during Study Visits 1 through 5, up to 6 weeks |
| Eastern Cooperative Oncology Group (ECOG) Score | The Eastern Cooperative Oncology Group (ECOG) score evaluates performance status of the participants by rating their ability to perform physical tasks and self care. Responses are 0 (fully active), 1 (restricted in physical strenuous activity but ambulatory), 2 (ambulatory and capable of all self-care but unable to carry out work activities), 3 (capable of only limited self-care), 4 (completely disabled), or 5 (dead). The ECOG score will be obtained at the baseline time point at each study visit where medication is administered. | Baseline during Visits 1 through 4, up to 4 weeks |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score | The PROMIS Global Health questionnaire, version 1.1, consists of 10 items assessing general domains of health and functioning. Items are scored on a 5-point scale where 1 = poor and 5 = excellent. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10. Scores above 50 indicate better health and functioning, while scores below 50 indicate physical, mental and social health that is below average. | Baseline during Visit 1 and Visit 5, up to 6 weeks |
The opioid sparing effect of NAS ketamine will be determined by evaluating total opioid consumption (rescue medication) prior to and during the study.
| Visit 1 through Visit 5, up to 6 weeks |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Cancer Type | Count of Participants | Participants |
|
| Pain Type | Count of Participants | Participants |
|
| OG000 |
| 10 mg Intranasal Ketamine |
Study participants receiving 10 mg of intranasal ketamine. |
| OG001 | 10 mg Intravenous (IV) Ketamine | Study participants receiving 10 mg of ketamine intravenously. |
| OG002 | 30 mg Intranasal Ketamine | Study participants receiving 30 mg of intranasal ketamine. |
| OG003 | 50 mg Intranasal Ketamine | Study participants receiving 50 mg of intranasal ketamine. |
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| Primary | Peak Concentration (Cmax) of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the peak concentration (Cmax) of intranasal and intravenous ketamine. Peak concentration is assessed as the maximum ng/mL of ketamine circulating in blood. Each study participant received each dose of ketamine during separate study visits. Samples were obtained at 2, 30, 60 and 240 minutes after medication administration. | This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome. | Posted | Geometric Mean | Standard Deviation | ng/ml | Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Area Under the Curve of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the elimination (a pharmacokinetic characteristic) of intranasal and intravenous ketamine. Elimination of the drug disappearing from the body is assessed as the area under the curve (AUC). Each study participant received each dose of ketamine during separate study visits. Samples were obtained at 2, 30, 60 and 240 minutes after medication administration. Each subject did not have quantitative levels at all time points. There were not enough data to construct a curve for each participant and therefore calculate an AUC. Data from all participants were naively pooled to calculate one AUC for the entire population (i.e., across all participants' data). | This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome. | Posted | Geometric Mean | Standard Deviation | micrograms•hour/Liter (µg•h/L) | Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks |
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| Primary | Time to Peak Concentration (Tmax) of Ketamine | Blood samples were obtained at the study visits where ketamine was administered to measure the time to peak concentration (Tmax) of intranasal and intravenous ketamine. Time is measured as minutes after administration when the maximum concentration of ketamine in blood is reached. | This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome. | Posted | Mean | Standard Deviation | minutes | Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Numerical Pain Rating Scale (NPRS) Score | The Numerical Pain Rating Scale (NPRS) was used to evaluate patient reported pain. Pain scores were recorded prior to and at 5,10,15, 30, 45, 60, 120, 180 and 240 minutes after administration of ketamine. The NPRS asks participants rate their current level of pain intensity on a scale from 0 (no pain) to 10 (worst possible pain). In general, improvements of pain severity of 1.5 points or less on NPRS could be seen as clinically irrelevant. Above that value, the cutoff point for "clinical relevance" depends on patients' baseline pain severity, and ranges from 2.4 to 5.3. Higher baseline scores require larger raw changes to represent clinically important differences. | Posted | Median | Inter-Quartile Range | units on a scale | Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score | To evaluate self-reported fatigue, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score | To evaluate self-reported dizziness, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score | To evaluate self-reported nausea, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score | To evaluate self-reported headache, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score | To evaluate self-reported feeling of unreality, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score | To evaluate self-reported change in hearing, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score | To evaluate self-reported change in vision, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score | To evaluate self-reported mood change, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score | To evaluate self-reported general discomfort, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score | To evaluate self-reported hallucinations, participants completed the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). During visits 1 through 4, side effects were documented by SERSDA prior to administration of medication and 30, 60 and 240 minutes after ketamine administration. Participants indicated the severity of this side effect by selecting 0 (side effect is absent), 1 (weak side effect), 2 (modest side effect), 3 (bothersome side effect), or 4 (side effect is very bothersome). | Posted | Mean | Standard Deviation | units on a scale | Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks |
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| Primary | Montgomery Asberg Depression Rating Scale (MADRS) Score | Depression was assessed on the Montgomery Asberg Depression Rating Scale (MADRS) during each study visit, before medication administration and 180 minutes after medication administration. The MADRS is designed to be particularly sensitive to treatment effects. The MADRS is a 10-item scale where the survey administrator rates the participant on a variety of aspects related to depression (such as apparent sadness, tension, and pessimistic thoughts) based on a clinical interview. Responses are provided on a scale of 0 to 6 where 0 signifies no difficulties in this area and 6 signifies severe difficulty. Total scores range from 0 to 60 with higher scores indicating greater severity of depression. | The MADRS assessment was only given at the baseline time point during the follow-up visit as no medication was administered during this visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks |
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| Primary | Edmonton Symptom Assessment System (ESAS) Score | The Edmonton Symptom Assessment System (ESAS) assesses nine symptoms that are common in cancer patients: pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and well-being. Each symptom is rated on a scale ranging from 0 (absence of symptom) to 10 (worst possible degree of symptom). The ESAS was administered at the baseline time point at each study visit. | Posted | Mean | Standard Deviation | units on a scale | Baseline during Study Visits 1 through 5, up to 6 weeks |
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| Primary | Eastern Cooperative Oncology Group (ECOG) Score | The Eastern Cooperative Oncology Group (ECOG) score evaluates performance status of the participants by rating their ability to perform physical tasks and self care. Responses are 0 (fully active), 1 (restricted in physical strenuous activity but ambulatory), 2 (ambulatory and capable of all self-care but unable to carry out work activities), 3 (capable of only limited self-care), 4 (completely disabled), or 5 (dead). The ECOG score will be obtained at the baseline time point at each study visit where medication is administered. | Posted | Mean | Standard Deviation | units on a scale | Baseline during Visits 1 through 4, up to 4 weeks |
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| Primary | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score | The PROMIS Global Health questionnaire, version 1.1, consists of 10 items assessing general domains of health and functioning. Items are scored on a 5-point scale where 1 = poor and 5 = excellent. Total scores are standardized to a T-score with a mean of 50 and a standard deviation of 10. Scores above 50 indicate better health and functioning, while scores below 50 indicate physical, mental and social health that is below average. | One participant did not complete the PROMIS questionnaire at the Follow-up Visit. | Posted | Mean | Standard Deviation | T-score | Baseline during Visit 1 and Visit 5, up to 6 weeks |
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| Secondary | Frequency of Rescue Medication Use | The opioid sparing effect of NAS ketamine will be determined by evaluating frequency of rescue medications use prior to and during the study. | Due to inconsistencies with participant-reported pill counts, the data for rescue medication use could not be reliably analyzed. | Posted | Visit 1 through Visit 5, up to 6 weeks |
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| Secondary | Total Opioid Consumption | The opioid sparing effect of NAS ketamine will be determined by evaluating total opioid consumption (rescue medication) prior to and during the study. | Due to inconsistencies with participant-reported pill counts, the data for total opioid consumption use could not be reliably analyzed. | Posted | Visit 1 through Visit 5, up to 6 weeks |
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| Post-Hoc | Systolic Blood Pressure | Blood pressure was measured at Baseline and up to 240 minutes after administration of ketamine. | Posted | Mean | Standard Deviation | millimeters of mercury (mmHg) | Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, 240, during Study Visits 1 through 4, up to 4 weeks |
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| Post-Hoc | Diastolic Blood Pressure | Blood pressure was measured at Baseline and up to 240 minutes after administration of ketamine. | Posted | Mean | Standard Deviation | mmHg | Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, 240, during Study Visits 1 through 4, up to 4 weeks |
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| Post-Hoc | Heart Rate | Heart rate was measured at Baseline and up to 240 minutes after administration of ketamine. | Posted | Mean | Standard Deviation | beats per minute | Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, 240, during Study Visits 1 through 4, up to 4 weeks |
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| 0 |
| 10 |
| 0 |
| 10 |
| 9 |
| 10 |
| EG001 | 10 mg Intravenous (IV) Ketamine | Study participants receiving 10 mg of ketamine intravenously. | 0 | 10 | 1 | 10 | 10 | 10 |
| EG002 | 30 mg Intranasal Ketamine | Study participants receiving 30 mg of intranasal ketamine. | 0 | 10 | 0 | 10 | 9 | 10 |
| EG003 | 50 mg Intranasal Ketamine | Study participants receiving 50 mg of intranasal ketamine. | 0 | 10 | 2 | 10 | 8 | 10 |
| EG004 | Follow-up Visit | Participants returned for a fifth visit to complete questionnaires. No study medication was administered during this visit. | 0 | 10 | 0 | 10 | 5 | 10 |
| EG005 | Phone Call 14 Days Post-Last Dose | Participants were called 14 days after the last dose of study medication to assess adverse events. | 0 | 10 | 0 | 10 | 2 | 10 |
| Non-cardiac chest pain | General disorders | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | Non-systematic Assessment |
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| Neck tumor swelling | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | Non-systematic Assessment |
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| Blurry vision | Eye disorders | Non-systematic Assessment |
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| Burning sensation in nostril | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Bradycardia | Cardiac disorders | Non-systematic Assessment |
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| Change in hearing | Ear and labyrinth disorders | Non-systematic Assessment |
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| Change in sense of smell | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Confusion | Psychiatric disorders | Non-systematic Assessment |
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| Dehydration | General disorders | Non-systematic Assessment |
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| Diaphoresis | Nervous system disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Dizziness | General disorders | Non-systematic Assessment |
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| Drowsiness | General disorders | Non-systematic Assessment |
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| Euphoria | General disorders | Non-systematic Assessment |
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| Facial numbnes | Nervous system disorders | Non-systematic Assessment |
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| Facial warmth | General disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Feeling of unreality | General disorders | Non-systematic Assessment |
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| Floating sensation | General disorders | Non-systematic Assessment |
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| Foul taste | General disorders | Non-systematic Assessment |
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| Fuzzy thinking | General disorders | Non-systematic Assessment |
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| Headache | General disorders | Non-systematic Assessment |
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| Hypertension | Vascular disorders | Non-systematic Assessment |
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| Hypotension | Vascular disorders | Non-systematic Assessment |
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| In touch with emotions | General disorders | Non-systematic Assessment |
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| Mood change | Psychiatric disorders | Non-systematic Assessment |
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| Nausea | General disorders | Non-systematic Assessment |
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| Night sweats | Nervous system disorders | Non-systematic Assessment |
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| Nightmares | General disorders | Non-systematic Assessment |
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| Restlessness | General disorders | Non-systematic Assessment |
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| Sinus tachycardia | Cardiac disorders | Non-systematic Assessment |
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| Somnolence | General disorders | Non-systematic Assessment |
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| Tongue numbness | Nervous system disorders | Non-systematic Assessment |
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| Vertigo | General disorders | Non-systematic Assessment |
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| Vision changes | Eye disorders | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Visual hallucination | General disorders | Non-systematic Assessment |
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| Intermittent nose bleeds | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Urinary retention | Renal and urinary disorders | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | Non-systematic Assessment |
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| Abdominal pain | General disorders | Non-systematic Assessment |
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Not provided
Not provided
Not provided
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
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