Cancer Cachexia
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of repeated oral administration of macimorelin at different doses daily for 1 week for the treatment of cancer cachexia.
Interventions
DRUGMacimorelin
Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.
DRUGPlacebo
placebo (Powerade®) daily for 7 days.
Sponsors
VA Office of Research and Development
Baylor College of Medicine
AEterna Zentaris
Garcia, Jose M., MD, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Subjects ≥18 years of age with histological diagnosis of incurable cancer (solid tumor), 2. ECOG performance status of 0-2, 3. Presence of cancer-related cachexia defined as an involuntary weight loss of at least 5% of the pre-illness body weight over the previous 6 months, and 4. Provide written informed consent prior to screening.
Exclusion criteria
1. Obesity (body weight \>140 Kg); 2. Recent active excessive alcohol or illicit drug use; 3. Severe depression as determined by the investigator; 4. Other causes of cachexia such as: Liver disease (AST or ALT \> 3x normal levels); renal failure (creatinine \>1.5 mg/dL), untreated thyroid disease, class III-IV CHF, AIDS, severe COPD requiring use of home O2; 5. Inability to increase food intake (e.g., esophageal obstruction, intractable nausea and vomiting); 6. Any condition that would prevent the subject from performing the research procedures (e.g. unstable coronary artery disease); 7. Use of growth hormone, megestrol, Marinol, or any other anabolic agents, appetite stimulants (including corticosteroids other than dexamethasone at the time of IV chemotherapy administrations), tube feeding, or parenteral nutrition during the 1 month prior to entering the study; 8. Recent administration (less than 1 week) of highly emetogenic chemotherapy (Hesketh scale class 4-5); subjects may otherwise be undergoing chemotherapy. 9. Being female and pregnant, breast-feeding or of childbearing potential. (Note: Lack of childbearing potential for female patients is satisfied by: a) being post menopausal; b) being surgically sterile; c) practicing contraception with an oral contraceptive, intra-uterine device, diaphragm, or condom with spermicide for the duration of the study; or d) being sexually inactive. Confirmation that the patient is not pregnant will be established by a negative serum hCG pregnancy test at the time of enrollment. 10. Co-administration of drugs that prolong QT interval, CYP3A4 inducers, QTc equal to or greater than 450ms at screening, or other investigational agents (a wash-out period of five times the half life of drugs that prolong QT will be allowed with approval of prescriber). 11. Conditions that would preclude from successfully scanning subjects in MRI: * Claustrophobia (this would make lying in the scanner very uncomfortable); b. having a pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants; c. History of Seizures d. History of head injuries resulting in loss of consciousness \> 10 minutes.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Body Weight | 7 days | The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1). |
| Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels | 7 days | The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7. |
| Change of Quality of Life Score | 7 days | The change of quality of life score (Anderson Symptom Assessment Scale \[ASAS; absolute score\], Functional Assessment of Chronic Illness-Fatigue \[FACIT-F; total score\]) will be measured between day 1 and day 7. The ASAS is a validated measure of quality of life (QOL) associated with symptom clusters commonly seen in cancer patient populations. The absolute score ranges from 0-100 with higher scores indicative of worse cancer symptoms. The FACIT-F is a validated measure of QOL associated with fatigue related to chronic illness. To account for missing items, the FACIT-F total score (sum of subscales) was adjusted by calculating the percent total score of items completed with the following: (FACIT-F Total Score)/(N items completed ×4 (maximum possible score for each item ) × 100% Scores range from 0 to 160 with higher scores indicative of greater fatigue. Tests consists of 5 subscales: Physical, Social/Family, Emotional, and Functional Well-Being, and Additional Concerns. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Energy Expenditure as Measured by Indirect Calorimetry. | 7 days | Change in energy expenditure as measured by indirect calorimetry. |
| Laboratory Assays | Day 1 to Day 7 | Change in Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3), Highly Sensitive C-Reactive Protein (CRP), and glucose between day 1 and day 7. |
| Safety Laboratory (White Blood Cells) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) |
| ECG | Day 1 to Day 7 | Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit. |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 7 days | Recording of any adverse events from day 1 to day 7. |
| Change in Stair Climbing Power (SCP) | Day 1 to Day 7 | SCP was assessed on Day 1 & 7. Participants were asked to climb a standard flight of hospital stairs (13 steps, 15.3 cm each) as quickly as possible, using the handrail if necessary. Two-three trials were attempted with one minute of rest in-between. The shortest completion time was transformed into power and used for analysis where: W= (body mass (kg) × acceleration of gravity (9.81 m⁄s\^2 )× vertical distance (1.99 m))/(time (seconds)) |
| Change in Percent Predicted Resting Energy Expenditure (REE) | Day 1 to Day 7 | Change in percent predicted (REE) as measured by indirect calorimetry. |
| Change in Respiratory Quotient | Day 1 to Day 7 | Change in respiratory quotient (the ratio of volume CO2 released to volume of O2 utilized) as measured by indirect calorimetry. |
| Laboratory Assays (Growth Hormone) | Day 1 to Day 7 | Change in Growth Hormone (GH) between day 1 and day 7. |
| Safety Laboratory (Red Blood Cells) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) |
| Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) and complete metabolic panel |
| Food Intake and Diary | 7 days | Food intake as measured by a food diary to be recorded for 3 days before days 1 and 7 and by a test meal done at screening and on day 7. |
| Safety Laboratory (Mean Corpuscular Volume [MCV]) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) |
| Safety Laboratory (Mean Corpuscular Hemoglobin [MCH]) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) |
| Safety Laboratory (Platelet) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) |
| Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete metabolic panel |
| Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete metabolic panel |
| Safety Laboratory (Potassium) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete metabolic panel |
| Safety Laboratory (Alkaline Phosphatase) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete metabolic panel |
| Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR]) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete metabolic panel |
| Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete metabolic panel |
| ECG (Heart Rate [HR]) | Day 1 to Day 7 | Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit. |
| Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Day 1 to Day 7 | Change in Clinical laboratory parameters: complete blood count (CBC) |
| Appetite (Visual Analog Scale [VAS] for Appetite) | 7 days | Change of appetite measured by a validated visual analogue scale between day 1 and day 7. The VAS is a one-item measure that quantifies subjective rating with a 100 mm line anchored at 0 mm with the words Not at all and at 100 mm with the word Extremely where the participant makes a mark on the line indicative of their current hunger level. Higher scores are indicative of greater perceived hunger. |
| Handgrip Strength | 7 days | Change in muscle strength as measured by handgrip strength. |
Countries
United States
Participant flow
Pre-assignment details
Trial was closed prior to target recruitment due to poor accrual and study relocation.
Participants by arm
| Arm | Count |
|---|---|
| Macimorelin Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days. | 9 |
| Placebo Placebo: placebo (Powerade®) daily for 7 days. | 4 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Macimorelin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Continuous | 70 years STANDARD_DEVIATION 6.8 | 66 years STANDARD_DEVIATION 6.5 | 66 years STANDARD_DEVIATION 6.4 |
| Anderson Symptom Assessment Scale (ASAS; absolute score) | 82 units on a scale STANDARD_DEVIATION 8.1 | 75 units on a scale STANDARD_DEVIATION 10.7 | 80 units on a scale STANDARD_DEVIATION 8.7 |
| BMI | 23.5 kg/m^2 STANDARD_DEVIATION 4 | 18.9 kg/m^2 STANDARD_DEVIATION 3.9 | 22.5 kg/m^2 STANDARD_DEVIATION 4.1 |
| Functional Assessment of Chronic Illness-Fatigue (FACIT-F; total score) | 70.0 units on a scale STANDARD_DEVIATION 10.9 | 65.0 units on a scale STANDARD_DEVIATION 10.4 | 70.0 units on a scale STANDARD_DEVIATION 10.6 |
| Height | 171.5 cm STANDARD_DEVIATION 8.2 | 167.6 cm STANDARD_DEVIATION 5.1 | 168.9 cm STANDARD_DEVIATION 7.2 |
| IGF-1 | 81 ng/mL STANDARD_DEVIATION 42.5 | 119 ng/mL STANDARD_DEVIATION 83.9 | 95 ng/mL STANDARD_DEVIATION 63.6 |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White, Hispanic | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized White, non-Hispanic | 5 Participants | 2 Participants | 7 Participants |
| Region of Enrollment United States | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 12 Participants |
| Weight | 65.3 kg STANDARD_DEVIATION 12.7 | 54.4 kg STANDARD_DEVIATION 9.9 | 63.5 kg STANDARD_DEVIATION 12.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 |
| other Total, other adverse events | 2 / 10 | 0 / 5 |
| serious Total, serious adverse events | 1 / 10 | 0 / 5 |
Outcome results
Primary
Change of Body Weight
The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Change of Body Weight | 0 kg | Standard Error 0.3 |
| Placebo | Change of Body Weight | 0.2 kg | Standard Error 0.2 |
Primary
Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels
The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels | 9 ng/mL | Standard Error 6.7 |
| Placebo | Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels | 23 ng/mL | Standard Error 3.9 |
Primary
Change of Quality of Life Score
The change of quality of life score (Anderson Symptom Assessment Scale \[ASAS; absolute score\], Functional Assessment of Chronic Illness-Fatigue \[FACIT-F; total score\]) will be measured between day 1 and day 7. The ASAS is a validated measure of quality of life (QOL) associated with symptom clusters commonly seen in cancer patient populations. The absolute score ranges from 0-100 with higher scores indicative of worse cancer symptoms. The FACIT-F is a validated measure of QOL associated with fatigue related to chronic illness. To account for missing items, the FACIT-F total score (sum of subscales) was adjusted by calculating the percent total score of items completed with the following: (FACIT-F Total Score)/(N items completed ×4 (maximum possible score for each item ) × 100% Scores range from 0 to 160 with higher scores indicative of greater fatigue. Tests consists of 5 subscales: Physical, Social/Family, Emotional, and Functional Well-Being, and Additional Concerns.
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Change of Quality of Life Score | ASAS | 13.5 score on a scale | Standard Deviation 5.1 |
| Macimorelin | Change of Quality of Life Score | FACIT-F | 0.9 score on a scale | Standard Deviation 4.7 |
| Placebo | Change of Quality of Life Score | ASAS | 6.7 score on a scale | Standard Deviation 7.8 |
| Placebo | Change of Quality of Life Score | FACIT-F | 0.2 score on a scale | Standard Deviation 5.3 |
Secondary
Appetite (Visual Analog Scale [VAS] for Appetite)
Change of appetite measured by a validated visual analogue scale between day 1 and day 7. The VAS is a one-item measure that quantifies subjective rating with a 100 mm line anchored at 0 mm with the words Not at all and at 100 mm with the word Extremely where the participant makes a mark on the line indicative of their current hunger level. Higher scores are indicative of greater perceived hunger.
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Appetite (Visual Analog Scale [VAS] for Appetite) | 7 units on a scale | Standard Error 11.3 |
| Placebo | Appetite (Visual Analog Scale [VAS] for Appetite) | -27.5 units on a scale | Standard Error 23.6 |
Secondary
Change in Percent Predicted Resting Energy Expenditure (REE)
Change in percent predicted (REE) as measured by indirect calorimetry.
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Change in Percent Predicted Resting Energy Expenditure (REE) | 4 % of predicted REE used | Standard Error 3.7 |
| Placebo | Change in Percent Predicted Resting Energy Expenditure (REE) | 3 % of predicted REE used | Standard Error 4.2 |
Secondary
Change in Respiratory Quotient
Change in respiratory quotient (the ratio of volume CO2 released to volume of O2 utilized) as measured by indirect calorimetry.
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Change in Respiratory Quotient | -0.01 Ratio | Standard Error 0.02 |
| Placebo | Change in Respiratory Quotient | -0.01 Ratio | Standard Error 0.01 |
Secondary
Change in Stair Climbing Power (SCP)
SCP was assessed on Day 1 & 7. Participants were asked to climb a standard flight of hospital stairs (13 steps, 15.3 cm each) as quickly as possible, using the handrail if necessary. Two-three trials were attempted with one minute of rest in-between. The shortest completion time was transformed into power and used for analysis where: W= (body mass (kg) × acceleration of gravity (9.81 m⁄s\^2 )× vertical distance (1.99 m))/(time (seconds))
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Change in Stair Climbing Power (SCP) | -5.1 W | Standard Error 8.8 |
| Placebo | Change in Stair Climbing Power (SCP) | -5.9 W | Standard Error 5.3 |
Secondary
ECG
Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | ECG | Pre-Dose PR Interval (ms) | 0 ms | Standard Error 4.3 |
| Macimorelin | ECG | Pre-Dose QRS Complex (ms) | 0 ms | Standard Error 1.2 |
| Macimorelin | ECG | Pre-Dose QT Interval (ms) | 5 ms | Standard Error 31.4 |
| Macimorelin | ECG | Pre-Dose QT Corrected for HR Interval (QTC; ms) | 3 ms | Standard Error 13.8 |
| Macimorelin | ECG | Post-Dose PR Interval (ms) | -4 ms | Standard Error 5.1 |
| Macimorelin | ECG | Post-Dose QRS Complex (ms) | 2 ms | Standard Error 1 |
| Macimorelin | ECG | Post-Dose QT Interval (ms) | 0 ms | Standard Error 8.8 |
| Macimorelin | ECG | Post-Dose QTC (ms) | 4 ms | Standard Error 3.5 |
| Placebo | ECG | Post-Dose QTC (ms) | -8.5 ms | Standard Error 17.3 |
| Placebo | ECG | Pre-Dose PR Interval (ms) | 2 ms | Standard Error 5.9 |
| Placebo | ECG | Post-Dose PR Interval (ms) | -4 ms | Standard Error 65.7 |
| Placebo | ECG | Pre-Dose QRS Complex (ms) | 3 ms | Standard Error 2.4 |
| Placebo | ECG | Post-Dose QT Interval (ms) | -17 ms | Standard Error 17.82 |
| Placebo | ECG | Pre-Dose QT Interval (ms) | -11 ms | Standard Error 13.4 |
| Placebo | ECG | Post-Dose QRS Complex (ms) | 3 ms | Standard Error 4.5 |
| Placebo | ECG | Pre-Dose QT Corrected for HR Interval (QTC; ms) | -4 ms | Standard Error 8.3 |
Secondary
ECG (Heart Rate [HR])
Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | ECG (Heart Rate [HR]) | Pre-Dose HR | 2.5 bpm | Standard Error 2.7 |
| Macimorelin | ECG (Heart Rate [HR]) | Post-Dose HR | -1 bpm | Standard Error 4.6 |
| Placebo | ECG (Heart Rate [HR]) | Post-Dose HR | 3 bpm | Standard Error 1.8 |
| Placebo | ECG (Heart Rate [HR]) | Pre-Dose HR | 2.5 bpm | Standard Error 2.9 |
Secondary
Energy Expenditure as Measured by Indirect Calorimetry.
Change in energy expenditure as measured by indirect calorimetry.
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Energy Expenditure as Measured by Indirect Calorimetry. | 49 kcals | Standard Error 51 |
| Placebo | Energy Expenditure as Measured by Indirect Calorimetry. | 34 kcals | Standard Error 49 |
Secondary
Food Intake and Diary
Food intake as measured by a food diary to be recorded for 3 days before days 1 and 7 and by a test meal done at screening and on day 7.
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Food Intake and Diary | Test Meal Caloric Intake | 59 kCals | Standard Error 123 |
| Macimorelin | Food Intake and Diary | Food Diary | -211 kCals | Standard Error 243.1 |
| Placebo | Food Intake and Diary | Test Meal Caloric Intake | -78 kCals | Standard Error 130 |
| Placebo | Food Intake and Diary | Food Diary | 96.1 kCals | Standard Error 343 |
Secondary
Handgrip Strength
Change in muscle strength as measured by handgrip strength.
Time frame: 7 days
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Handgrip Strength | 1.3 kg | Standard Error 0.9 |
| Placebo | Handgrip Strength | 1.4 kg | Standard Error 0.5 |
Secondary
Laboratory Assays
Change in Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3), Highly Sensitive C-Reactive Protein (CRP), and glucose between day 1 and day 7.
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Laboratory Assays | IGFBP-3 | 0.25 mcg/mL | Standard Error 0.1 |
| Macimorelin | Laboratory Assays | hs-CRP | -0.5 mcg/mL | Standard Error 0.4 |
| Macimorelin | Laboratory Assays | Glucose | 10 mcg/mL | Standard Error 230 |
| Placebo | Laboratory Assays | IGFBP-3 | 0.1 mcg/mL | Standard Error 0.2 |
| Placebo | Laboratory Assays | hs-CRP | -0.4 mcg/mL | Standard Error 0.4 |
| Placebo | Laboratory Assays | Glucose | -35 mcg/mL | Standard Error 95 |
Secondary
Laboratory Assays (Growth Hormone)
Change in Growth Hormone (GH) between day 1 and day 7.
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy); one patient in macimorelin (0.5 mg/kg) discontinued the study after receiving two doses due to non-compliance. Final number included for analysis was Macimorelin, N=9 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Laboratory Assays (Growth Hormone) | 0.7 ng/mL | Standard Error 1.2 |
| Placebo | Laboratory Assays (Growth Hormone) | -0.5 ng/mL | Standard Error 1 |
Secondary
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil)
Change in Clinical laboratory parameters: complete blood count (CBC)
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Neutrophil | 5.9 % of cells | Standard Error 7.2 |
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Monocyte | 0.9 % of cells | Standard Error 2 |
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | RCDW | 0 % of cells | Standard Error 0.3 |
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Eosinophil | -0.1 % of cells | Standard Error 1.3 |
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Lymphocyte | -0.1 % of cells | Standard Error 5.5 |
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Basophil | 0.1 % of cells | Standard Error 0.1 |
| Macimorelin | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | HCT | 0.7 % of cells | Standard Error 0.8 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Basophil | 0.7 % of cells | Standard Error 0.3 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | HCT | -2.3 % of cells | Standard Error 1 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | RCDW | 0 % of cells | Standard Error 0.2 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Neutrophil | 1.2 % of cells | Standard Error 11.4 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Lymphocyte | 0.4 % of cells | Standard Error 7.3 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Monocyte | -0.8 % of cells | Standard Error 0.8 |
| Placebo | Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) | Eosinophil | -0.7 % of cells | Standard Error 3.1 |
Secondary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Recording of any adverse events from day 1 to day 7.
Time frame: 7 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Macimorelin | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Non-Serious, Unrelated Adverse Event | 2 Participants |
| Macimorelin | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Unrelated, Serious Adverse Event | 1 Participants |
| Placebo | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Non-Serious, Unrelated Adverse Event | 0 Participants |
| Placebo | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Unrelated, Serious Adverse Event | 0 Participants |
Secondary
Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST])
Change in Clinical laboratory parameters: complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) | ALT | -2 U/L | Standard Error 2.5 |
| Macimorelin | Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) | AST | 0.5 U/L | Standard Error 5.9 |
| Placebo | Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) | ALT | 0 U/L | Standard Error 0.6 |
| Placebo | Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) | AST | 1.5 U/L | Standard Error 1.4 |
Secondary
Safety Laboratory (Alkaline Phosphatase)
Change in Clinical laboratory parameters: complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Alkaline Phosphatase) | 3 IU/L | Standard Error 5.4 |
| Placebo | Safety Laboratory (Alkaline Phosphatase) | -4 IU/L | Standard Error 4.3 |
Secondary
Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium)
Change in Clinical laboratory parameters: complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | BUN | -1.5 mg/dL | Standard Error 1.3 |
| Macimorelin | Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | Creatinine | 0 mg/dL | Standard Error 0.1 |
| Macimorelin | Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | Calcium | 0.2 mg/dL | Standard Error 0.3 |
| Placebo | Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | BUN | 2 mg/dL | Standard Error 0.9 |
| Placebo | Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | Creatinine | -0.03 mg/dL | Standard Error 0 |
| Placebo | Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) | Calcium | 0 mg/dL | Standard Error 0.1 |
Secondary
Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR])
Change in Clinical laboratory parameters: complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR]) | -3.9 mL/min/1.73 m^2 | Standard Error 4.8 |
| Placebo | Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR]) | 3.4 mL/min/1.73 m^2 | Standard Error 4.3 |
Secondary
Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin)
Change in Clinical laboratory parameters: complete blood count (CBC) and complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | HGB | 0.3 g/dL | Standard Error 0.2 |
| Macimorelin | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | MCH Concentration | 0.3 g/dL | Standard Error 0.2 |
| Macimorelin | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | Protein | 0.3 g/dL | Standard Error 0.7 |
| Macimorelin | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | Total Albumin | 0.1 g/dL | Standard Error 0.3 |
| Placebo | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | Total Albumin | -0.1 g/dL | Standard Error 0.6 |
| Placebo | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | HGB | -0.7 g/dL | Standard Error 0.4 |
| Placebo | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | Protein | -0.3 g/dL | Standard Error 0.2 |
| Placebo | Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) | MCH Concentration | 0.4 g/dL | Standard Error 0.2 |
Secondary
Safety Laboratory (Mean Corpuscular Hemoglobin [MCH])
Change in Clinical laboratory parameters: complete blood count (CBC)
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Mean Corpuscular Hemoglobin [MCH]) | 0.2 pg | Standard Error 0.2 |
| Placebo | Safety Laboratory (Mean Corpuscular Hemoglobin [MCH]) | 0.3 pg | Standard Error 0.1 |
Secondary
Safety Laboratory (Mean Corpuscular Volume [MCV])
Change in Clinical laboratory parameters: complete blood count (CBC)
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Mean Corpuscular Volume [MCV]) | -0.1 fl | Standard Error 7 |
| Placebo | Safety Laboratory (Mean Corpuscular Volume [MCV]) | -0.2 fl | Standard Error 0.4 |
Secondary
Safety Laboratory (Platelet)
Change in Clinical laboratory parameters: complete blood count (CBC)
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Platelet) | 14.5 10^3 cells/mcL | Standard Error 21.9 |
| Placebo | Safety Laboratory (Platelet) | 10.5 10^3 cells/mcL | Standard Error 9.3 |
Secondary
Safety Laboratory (Potassium)
Change in Clinical laboratory parameters: complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Potassium) | 0 mmol/L | Standard Error 0.1 |
| Placebo | Safety Laboratory (Potassium) | -0.4 mmol/L | Standard Error 0.6 |
Secondary
Safety Laboratory (Red Blood Cells)
Change in Clinical laboratory parameters: complete blood count (CBC)
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (Red Blood Cells) | 0.1 10^6 cells/mcL | Standard Error 0.1 |
| Placebo | Safety Laboratory (Red Blood Cells) | -0.4 10^6 cells/mcL | Standard Error 0.1 |
Secondary
Safety Laboratory (Sodium; Chloride; Carbon Dioxide)
Change in Clinical laboratory parameters: complete metabolic panel
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Macimorelin | Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Sodium | 0 mEq/L | Standard Error 0.9 |
| Macimorelin | Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Chloride | -1 mEq/L | Standard Error 1.3 |
| Macimorelin | Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Carbon Dioxide | 0 mEq/L | Standard Error 0.7 |
| Placebo | Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Sodium | 1 mEq/L | Standard Error 0.9 |
| Placebo | Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Chloride | 2 mEq/L | Standard Error 1.5 |
| Placebo | Safety Laboratory (Sodium; Chloride; Carbon Dioxide) | Carbon Dioxide | -2 mEq/L | Standard Error 1.5 |
Secondary
Safety Laboratory (White Blood Cells)
Change in Clinical laboratory parameters: complete blood count (CBC)
Time frame: Day 1 to Day 7
Population: One patient in placebo discontinued the study after one dose due to initiation of an exclusionary medication (QT-prolonging chemotherapy). Final number included for analysis was Macimorelin, N=10 and Placebo N=4
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Macimorelin | Safety Laboratory (White Blood Cells) | 0.2 10^9 cells/L | Standard Error 0.5 |
| Placebo | Safety Laboratory (White Blood Cells) | 0.6 10^9 cells/L | Standard Error 1.4 |