Intranasal (NAS) Ketamine for Cancer Pain

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03146806
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 32.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer; Pain	Drug: Intranasal ketamine	Phase 1/Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer Related Pain
• Actual Study Start Date: Jul 25, 2017
• Actual Primary Completion Date: Apr 22, 2020
• Actual Study Completion Date: Apr 22, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intranasal ketamine treatment Study participants who are receiving intranasal ketamine treatments.

Drug: Intranasal ketamine; 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.; Other Names: NAS ketamine Ketamine hydrochloride (HCl) intranasal

Outcome Measures

Primary Outcome Measures

1. Bioavailability of Ketamine [Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks]

   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.

2. Peak Concentration (Cmax) of Ketamine [Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks]

   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.

3. Area Under the Curve of Ketamine [Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks]

   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).

4. Time to Peak Concentration (Tmax) of Ketamine [Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks]

   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.

5. Numerical Pain Rating Scale (NPRS) Score [Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks]

   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.

6. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

   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).

7. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

   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).

8. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

   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).

9. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

   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).

10. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

    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).

11. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

    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).

12. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

    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).

13. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

    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).

14. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

    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).

15. Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score [Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks]

    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).

16. Montgomery Asberg Depression Rating Scale (MADRS) Score [Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks]

    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.

17. Edmonton Symptom Assessment System (ESAS) Score [Baseline during Study Visits 1 through 5, up to 6 weeks]

    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.

18. Eastern Cooperative Oncology Group (ECOG) Score [Baseline during Visits 1 through 4, up to 4 weeks]

    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.

19. Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score [Baseline during Visit 1 and Visit 5, up to 6 weeks]

    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.

Secondary Outcome Measures

1. Frequency of Rescue Medication Use [Visit 1 through Visit 5, up to 6 weeks]

   The opioid sparing effect of NAS ketamine will be determined by evaluating frequency of rescue medications use prior to and during the study.

2. Total Opioid Consumption [Visit 1 through 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with uncontrolled pain related to cancer or cancer treatment. Uncontrolled pain will be defined as:

• Pain which persists for more than 7 days and is rated >/=4 on Numerical Pain Rating Score (NPRS)

• Use of breakthrough medication more than 4 times in 24 hours or being treated with oral morphine equivalent of 50 mg/d or more

• 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:

• Use of oral, injected or implanted hormonal methods of contraception or;

• Placement of an intrauterine device (IUD) or intrauterine system (IUS);

• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;

• Total abstinence or;

• Male/female sterilization.

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Winship Cancer Institute	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University

Investigators

• Principal Investigator: Vinita Singh, MD, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 1, 2019

More Information

Publications

• 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.

• Responsible Party: Vinita Singh, Assistant Professor, Emory University
• ClinicalTrials.gov Identifier: NCT03146806
• Other Study ID Numbers: IRB00086610
• First Posted: May 10, 2017
• Last Update Posted: Sep 9, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Vinita Singh, Assistant Professor, Emory University: Cancer pain; Anesthesiology; Opiates; Intranasal ketamine
• Additional relevant MeSH terms: Cancer Pain; Ketamine

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Ketamine Treatment
Arm/Group Description	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.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Intranasal Ketamine Treatment
Arm/Group Description	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.
Overall Participants	10
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	49.5
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%
Not Hispanic or Latino	9 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 30%
White	7 70%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%
Cancer Type (Count of Participants)
Breast	4 40%
Bone	2 20%
Lung	1 10%
Colon	1 10%
Larynx	1 10%
Multiple myeloma	1 10%
Pain Type (Count of Participants)
Nociceptive	5 50%
Neuropathic	0 0%
Mixed nociceptive and neuropathic pain	5 50%

Outcome Measures

1. Primary Outcome

Title	Bioavailability of Ketamine
Description	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.
Time Frame	Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	7	9	10	10
Baseline	0 (0)	0 (0)	0 (0)
2 minutes post-ketamine administration	13.4 (1.65)	296.4 (1.71)	23.7 (2.98)	33.7 (3.86)
30 minutes post-ketamine administration	20.3 (2.01)	35.0 (1.35)	48.6 (1.67)	51.0 (1.75)
60 minutes post-ketamine administration	11.7 (1.38)	16.4 (1.70)	26.5 (2.1)	55.8 (2.12)
240 minutes post-ketamine administration	0 (0)	0 (0)	0 (0)	0 (0)

2. Primary Outcome

Title	Peak Concentration (Cmax) of Ketamine
Description	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.
Time Frame	Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	7	9	10	10
Geometric Mean (Standard Deviation) [ng/ml]	22.9 (1.97)	296 (1.71)	60.8 (1.90)	77.6 (2.29)

3. Primary Outcome

Title	Area Under the Curve of Ketamine
Description	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).
Time Frame	Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks

Outcome Measure Data

Analysis Population Description

This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	7	9	10	10
Geometric Mean (Standard Deviation) [micrograms•hour/Liter (µg•h/L)]	19 (NA)	113 (NA)	46 (NA)	64 (NA)

4. Primary Outcome

Title	Time to Peak Concentration (Tmax) of Ketamine
Description	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.
Time Frame	Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

This analysis includes participants with viable samples. Some samples were not able to be reliably analyzed for this outcome.

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	7	9	10	10
Mean (Standard Deviation) [minutes]	23 (3.0)	2 (1)	14 (3.8)	16 (4.4)

5. Primary Outcome

Title	Numerical Pain Rating Scale (NPRS) Score
Description	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.
Time Frame	Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	7.5	6	5.5	6
Minute 5	6	1	5	5
Minute 10	6	0	3	4
Minute 15	5	1.5	3.5	3
Minute 30	4.5	2.5	3.5	2
Minute 45	5	3	3	2
Minute 60	4.5	3.5	2.5	2
Minute 120	4.5	3.5	3	2
Minute 180	5	4	3	2.5
Minute 240	5	3	3	5

6. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	2.9 (0.86)	1.4 (0.84)	1.6 (0.70)	1.5 (1.27)
Minute 30	1 (1.15)	1.6 (1.17)	1.3 (1.06)	1.0 (1.25)
Minute 60	0.7 (0.95)	1.2 (1.23)	1.2 (1.14)	1.2 (1.03)
Minute 240	0.8 (0.92)	1 (0.82)	0.8 (1.03)	0.7 (0.67)

7. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0.6 (0.97)	0.1 (0.32)	0 (0)	0 (0)
Minute 30	0.1 (0.32)	0.8 (1.14)	0.3 (0.67)	0.5 (0.71)
Minute 60	0 (0)	0.3 (0.95)	0.1 (0.32)	0.2 (0.63)
Minute 240	0 (0)	0 (0)	0 (0)	0 (0)

8. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0.2 (0.42)	0.3 (0.67)	0.1 (0.32)	0.1 (0.32)
Minute 30	0.3 (0.95)	0.8 (1.32)	0.4 (0.97)	0.3 (0.67)
Minute 60	0.2 (0.63)	0.6 (1.07)	0.1 (0.32)	0.3 (0.67)
Minute 240	0.1 (0.32)	0 (0)	0.4 (0.97)	0.4 (1.26)

9. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0.2 (0.63)	0 (0)	0 (0)	0 (0)
Minute 30	0 (0)	0.1 (0.32)	0 (0)	0 (0)
Minute 60	0 (0)	0.1 (0.32)	0 (0)	0 (0)
Minute 240	0 (0)	0 (0)	0 (0)	0 (0)

10. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0.2 (0.63)	0 (0)	0 (0)	0 (0)
Minute 30	0.4 (1.26)	1.3 (1.42)	0.2 (0.42)	0.2 (0.42)
Minute 60	0 (0)	0.5 (1.27)	0 (0)	0.1 (0.32)
Minute 240	0 (0)	0.2 (0.63)	0 (0)	0 (0)

11. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0 (0)	0 (0)	0.1 (0.32)	0 (0)
Minute 30	0 (0)	0.1 (0.32)	0 (0)	0 (0)
Minute 60	0 (0)	0 (0)	0 (0)	0 (0)
Minute 240	0 (0)	0.3 (0.95)	0 (0)	0 (0)

12. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0.4 (0.70)	0.1 (0.32)	0.1 (0.32)	0 (0)
Minute 30	0.1 (0.32)	0.5 (0.85)	0.1 (0.32)	0.1 (0.21)
Minute 60	0 (0)	0.1 (0.32)	0 (0)	0.1 (0.32)
Minute 240	0 (0)	0 (0)	0 (0)	0 (0)

13. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0.5 (0.85)	0 (0)	0 (0)	0.5 (1.08)
Minute 30	0 (0)	0.6 (1.26)	0.1 (0.32)	0.4 (0.70)
Minute 60	0 (0)	0.4 (1.26)	0 (0)	0.1 (0.32)
Minute 240	0 (0)	0 (0)	0 (0)	0.3 (0.67)

14. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	1.6 (1.51)	1.3 (1.34)	1.2 (1.32)	1.1 (1.45)
Minute 30	0.9 (1.37)	1.1 (1.45)	0.8 (1.32)	0.8 (1.14)
Minute 60	0.6 (1.35)	0.8 (1.32)	0.8 (1.32)	0.8 (1.32)
Minute 240	0.5 (1.08)	0.8 (1.32)	0.8 (1.32)	1.2 (1.62)

15. Primary Outcome

Title	Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score
Description	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).
Time Frame	Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	0 (0)	0 (0)	0 (0)	0 (0)
Minute 30	0 (0)	0 (0)	0 (0)	0 (0)
Minute 60	0 (0)	0 (0)	0 (0)	0 (0)
Minute 240	0 (0)	0 (0)	0 (0)	0 (0)

16. Primary Outcome

Title	Montgomery Asberg Depression Rating Scale (MADRS) Score
Description	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.
Time Frame	Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks

Outcome Measure Data

Analysis Population Description

The MADRS assessment was only given at the baseline time point during the follow-up visit as no medication was administered during this visit.

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine	Follow-up Visit
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.	Participants returned for a fifth visit to complete questionnaires. No study medication was administered during this visit.
Measure Participants	10	10	10	10	10
Baseline	18.7 (6.57)	13.4 (6.40)	12 (5.05)	11.89 (8.34)	14.78 (7.31)
Minute 180	13.5 (4.38)	13.3 (5.31)	11.3 (6.15)	9.67 (8.34)

17. Primary Outcome

Title	Edmonton Symptom Assessment System (ESAS) Score
Description	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.
Time Frame	Baseline during Study Visits 1 through 5, up to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine	Follow-up Visit
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.	Participants returned for a fifth visit to complete questionnaires. No study medication was administered during this visit.
Measure Participants	10	10	10	10	10
Pain	6.64 (1.96)	6.27 (2.10)	5.80 (1.81)	5.73 (2.53)	5.30 (1.89)
Tiredness	6.09 (1.92)	4.73 (2.57)	4.20 (2.44)	4.36 (2.54)	3.60 (2.11)
Drowsiness	4.64 (2.98)	3.64 (2.58)	2.90 (2.60)	3.64 (2.50)	2.00 (2.21)
Nausea	1.09 (2.59)	0.82 (1.60)	0.40 (0.70)	0.227 (0.65)	0 (0)
Lack of Appetite	4.55 (2.77)	3.45 (2.38)	3.00 (3.02)	2.20 (2.10)	2.20 (2.20)
Shortness of Breath	1.55 (2.70)	1.09 (1.97)	0.40 (1.26)	0.18 (0.60)	0.60 (0.97)
Depression	3.18 (2.44)	2.45 (1.86)	1.50 (1.51)	0.82 (1.33)	2.10 (3.41)
Anxiety	3.82 (2.82)	2.82 (1.94)	1.00 (1.25)	1.27 (1.68)	0.60 (0.97)
Well-being	4.82 (2.52)	4.45 (2.88)	4.20 (2.20)	4.09 (2.66)	4.60 (2.27)

18. Primary Outcome

Title	Eastern Cooperative Oncology Group (ECOG) Score
Description	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.
Time Frame	Baseline during Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Mean (Standard Deviation) [units on a scale]	2.1 (0.88)	2.1 (0.88)	1.8 (0.79)	1.9 (0.99)

19. Primary Outcome

Title	Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score
Description	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.
Time Frame	Baseline during Visit 1 and Visit 5, up to 6 weeks

Outcome Measure Data

Analysis Population Description

One participant did not complete the PROMIS questionnaire at the Follow-up Visit.

Arm/Group Title	Visit 1 (10 mg Intranasal Ketamine Administered)	Follow-up Visit
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Participants returned for a fifth visit to complete questionnaires. No study medication was administered during this visit.
Measure Participants	10	9
Physical T-Score	35.5 (5.70)	33.96 (4.24)
Mental T-Score	43.02 (4.17)	40.52 (7.26)

20. Secondary Outcome

Title	Frequency of Rescue Medication Use
Description	The opioid sparing effect of NAS ketamine will be determined by evaluating frequency of rescue medications use prior to and during the study.
Time Frame	Visit 1 through Visit 5, up to 6 weeks

Outcome Measure Data

Analysis Population Description

Due to inconsistencies with participant-reported pill counts, the data for rescue medication use could not be reliably analyzed.

Arm/Group Title	Intranasal Ketamine Treatment
Arm/Group Description	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.
Measure Participants	0

21. Secondary Outcome

Title	Total Opioid Consumption
Description	The opioid sparing effect of NAS ketamine will be determined by evaluating total opioid consumption (rescue medication) prior to and during the study.
Time Frame	Visit 1 through Visit 5, up to 6 weeks

Outcome Measure Data

Analysis Population Description

Due to inconsistencies with participant-reported pill counts, the data for total opioid consumption use could not be reliably analyzed.

Arm/Group Title	Intranasal Ketamine Treatment
Arm/Group Description	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.
Measure Participants	0

22. Post-Hoc Outcome

Title	Systolic Blood Pressure
Description	Blood pressure was measured at Baseline and up to 240 minutes after administration of ketamine.
Time Frame	Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	118.6 (19.7)	117.5 (20.8)	117.6 (20.0)	115.8 (19.3)
Minute 5	117.8 (19.2)	134.4 (30.7)	119.9 (20.0)	118.3 (14.8)
Minute 10	122.3 (19.0)	129.6 (23.3)	122.9 (20.2)	120.2 (19.1)
Minute 15	119.0 (23.0)	124.0 (20.9)	123.1 (25.0)	123.1 (16.9)
Minute 30	121.7 (22.0)	117.2 (20.6)	125.4 (23.0)	124.9 (18.1)
Minute 45	119.8 (22.3)	117.4 (15.1)	121.3 (18.5)	117.0 (18.4)
Minute 60	116.9 (19.4)	114.1 (13.4)	118.7 (20.8)	118.6 (17.4)
Minute 120	117.2 (18.9)	111.5 (13.4)	114.9 (17.8)	111.5 (13.0)
Minute 180	111.9 (24.7)	115.9 (15.5)	116.3 (19.3)	111.7 (13.2)
Minute 240	116.2 (23.4)	111.7 (12.9)	118.2 (19.4)	116.5 (23.9)

23. Post-Hoc Outcome

Title	Diastolic Blood Pressure
Description	Blood pressure was measured at Baseline and up to 240 minutes after administration of ketamine.
Time Frame	Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	72.5 (7.2)	76.3 (10.7)	73.5 (9.8)	72.2 (9.0)
Minute 5	73.0 (9.1)	82.4 (11.0)	72.1 (9.4)	74.4 (10.1)
Minute 10	76.6 (7.9)	81.1 (6.4)	75.2 (9.8)	73.2 (11.8)
Minute 15	73.4 (6.8)	78.5 (6.3)	74.1 (10.6)	76.8 (8.3)
Minute 30	74.3 (6.7)	72.2 (8.1)	75.9 (11.2)	77.1 (8.6)
Minute 45	74.8 (7.4)	71.7 (12.3)	75.5 (10.8)	73.4 (8.8)
Minute 60	73.0 (7.3)	73.6 (6.3)	75.4 (11.3)	73.4 (10.5)
Minute 120	72.9 (8.9)	72.9 (7.3)	72.1 (7.5)	72.2 (8.1)
Minute 180	69.1 (11.1)	71.9 (6.1)	69.0 (6.5)	70.8 (10.0)
Minute 240	73.3 (7.32)	70.2 (5.5)	72.7 (6.4)	75.3 (11.9)

24. Post-Hoc Outcome

Title	Heart Rate
Description	Heart rate was measured at Baseline and up to 240 minutes after administration of ketamine.
Time Frame	Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, 240, during Study Visits 1 through 4, up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	10 mg Intranasal Ketamine	10 mg Intravenous (IV) Ketamine	30 mg Intranasal Ketamine	50 mg Intranasal Ketamine
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.	Study participants receiving 10 mg of ketamine intravenously.	Study participants receiving 30 mg of intranasal ketamine.	Study participants receiving 50 mg of intranasal ketamine.
Measure Participants	10	10	10	10
Baseline	80.0 (19.6)	82.2 (18.4)	81.3 (16.0)	79.5 (14.6)
Minute 5	80.4 (19.6)	84.3 (18.2)	76.7 (14.2)	79.9 (13.6)
Minute 10	78.9 (17.0)	81.1 (15.2)	75.7 (12.7)	79.7 (14.5)
Minute 15	77.3 (15.4)	78.4 (16.2)	76.6 (13.0)	81.6 (15.5)
Minute 30	79.1 (17.2)	75.3 (13.2)	74.2 (12.0)	81.2 (16.4)
Minute 45	78.7 (17.7)	73.2 (17.5)	75.2 (12.0)	79.7 (15.0)
Minute 60	75.9 (16.5)	74.4 (14.2)	75.8 (13.6)	80.3 (16.0)
Minute 120	81.6 (18.7)	78.5 (17.9)	76.1 (16.2)	78.9 (15.9)
Minute 180	79.1 (20.4)	76.7 (15.6)	78.0 (16.7)	80.0 (16.0)
Minute 240	80.9 (21.6)	80.2 (17.8)	74.0 (13.6)	79.8 (14.2)

Adverse Events

Time Frame	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.
Arm/Group Title	10 mg Intranasal Ketamine		10 mg Intravenous (IV) Ketamine		30 mg Intranasal Ketamine		50 mg Intranasal Ketamine		Follow-up Visit		Phone Call 14 Days Post-Last Dose
Arm/Group Description	Study participants receiving 10 mg of intranasal ketamine.		Study participants receiving 10 mg of ketamine intravenously.		Study participants receiving 30 mg of intranasal ketamine.		Study participants receiving 50 mg of intranasal ketamine.		Participants returned for a fifth visit to complete questionnaires. No study medication was administered during this visit.		Participants were called 14 days after the last dose of study medication to assess adverse events.
All Cause Mortality
	10 mg Intranasal Ketamine		10 mg Intravenous (IV) Ketamine		30 mg Intranasal Ketamine		50 mg Intranasal Ketamine		Follow-up Visit		Phone Call 14 Days Post-Last Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Serious Adverse Events
	10 mg Intranasal Ketamine		10 mg Intravenous (IV) Ketamine		30 mg Intranasal Ketamine		50 mg Intranasal Ketamine		Follow-up Visit		Phone Call 14 Days Post-Last Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/10 (10%)		0/10 (0%)		2/10 (20%)		0/10 (0%)		0/10 (0%)
General disorders
Abdominal pain	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Non-cardiac chest pain	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Infections and infestations
Pneumonia	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neck tumor swelling	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	10 mg Intranasal Ketamine		10 mg Intravenous (IV) Ketamine		30 mg Intranasal Ketamine		50 mg Intranasal Ketamine		Follow-up Visit		Phone Call 14 Days Post-Last Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/10 (90%)		10/10 (100%)		9/10 (90%)		8/10 (80%)		5/10 (50%)		2/10 (20%)
Cardiac disorders
Bradycardia	1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Sinus tachycardia	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)
Ear and labyrinth disorders
Change in hearing	0/10 (0%)		2/10 (20%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Eye disorders
Blurry vision	1/10 (10%)		2/10 (20%)		1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Vision changes	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Gastrointestinal disorders
Diarrhea	0/10 (0%)		1/10 (10%)		0/10 (0%)		2/10 (20%)		1/10 (10%)		0/10 (0%)
Vomiting	0/10 (0%)		2/10 (20%)		0/10 (0%)		2/10 (20%)		0/10 (0%)		0/10 (0%)
General disorders
Dehydration	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		1/10 (10%)		0/10 (0%)
Dizziness	1/10 (10%)		6/10 (60%)		3/10 (30%)		4/10 (40%)		0/10 (0%)		0/10 (0%)
Drowsiness	2/10 (20%)		1/10 (10%)		1/10 (10%)		3/10 (30%)		0/10 (0%)		0/10 (0%)
Euphoria	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Facial warmth	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Fatigue	1/10 (10%)		2/10 (20%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Feeling of unreality	1/10 (10%)		6/10 (60%)		3/10 (30%)		1/10 (10%)		1/10 (10%)		0/10 (0%)
Floating sensation	0/10 (0%)		1/10 (10%)		1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Foul taste	1/10 (10%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Fuzzy thinking	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Headache	0/10 (0%)		2/10 (20%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
In touch with emotions	0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Nausea	1/10 (10%)		4/10 (40%)		1/10 (10%)		2/10 (20%)		0/10 (0%)		0/10 (0%)
Nightmares	0/10 (0%)		1/10 (10%)		1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Restlessness	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Somnolence	0/10 (0%)		1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Vertigo	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Visual hallucination	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)
Abdominal pain	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)
Infections and infestations
Urinary tract infection	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)
Nervous system disorders
Diaphoresis	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Facial numbnes	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Night sweats	0/10 (0%)		1/10 (10%)		1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)
Tongue numbness	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Psychiatric disorders
Agitation	0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Anxiety	0/10 (0%)		2/10 (20%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Confusion	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Mood change	0/10 (0%)		2/10 (20%)		1/10 (10%)		2/10 (20%)		0/10 (0%)		0/10 (0%)
Renal and urinary disorders
Urinary retention	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Burning sensation in nostril	1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Change in sense of smell	0/10 (0%)		0/10 (0%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)
Skin and subcutaneous tissue disorders
Intermittent nose bleeds	0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		0/10 (0%)		1/10 (10%)
Vascular disorders
Hypertension	2/10 (20%)		2/10 (20%)		2/10 (20%)		4/10 (40%)		0/10 (0%)		0/10 (0%)
Hypotension	2/10 (20%)		1/10 (10%)		1/10 (10%)		0/10 (0%)		0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.