Trial Outcomes & Findings for Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia (NCT NCT01614990)

NCT ID: NCT01614990

Last Updated: 2024-03-20

Results Overview

The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 15 participants
• Primary outcome timeframe: 7 days
• Results posted on: 2024-03-20

Participant Flow

Trial was closed prior to target recruitment due to poor accrual and study relocation.

Participant milestones

Measure	Macimorelin Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo Placebo: placebo (Powerade®) daily for 7 days.
Overall Study STARTED	10	5
Overall Study COMPLETED	9	4
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Macimorelin Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo Placebo: placebo (Powerade®) daily for 7 days.
Overall Study Protocol Violation	1	1

Baseline Characteristics

Pilot Clinical Trial of Repeated Doses of Macimorelin to Assess Safety and Efficacy in Patients With Cancer Cachexia

Baseline characteristics by cohort

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	70 years STANDARD_DEVIATION 6.8 • n=5 Participants	66 years STANDARD_DEVIATION 6.5 • n=7 Participants	66 years STANDARD_DEVIATION 6.4 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized White, non-Hispanic	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White, Hispanic	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
BMI	23.5 kg/m^2 STANDARD_DEVIATION 4.0 • n=5 Participants	18.9 kg/m^2 STANDARD_DEVIATION 3.9 • n=7 Participants	22.5 kg/m^2 STANDARD_DEVIATION 4.1 • n=5 Participants
Height	171.5 cm STANDARD_DEVIATION 8.2 • n=5 Participants	167.6 cm STANDARD_DEVIATION 5.1 • n=7 Participants	168.9 cm STANDARD_DEVIATION 7.2 • n=5 Participants
Weight	65.3 kg STANDARD_DEVIATION 12.7 • n=5 Participants	54.4 kg STANDARD_DEVIATION 9.9 • n=7 Participants	63.5 kg STANDARD_DEVIATION 12.2 • n=5 Participants
IGF-1	81 ng/mL STANDARD_DEVIATION 42.5 • n=5 Participants	119 ng/mL STANDARD_DEVIATION 83.9 • n=7 Participants	95 ng/mL STANDARD_DEVIATION 63.6 • n=5 Participants
Anderson Symptom Assessment Scale (ASAS; absolute score)	82 units on a scale STANDARD_DEVIATION 8.1 • n=5 Participants	75 units on a scale STANDARD_DEVIATION 10.7 • n=7 Participants	80 units on a scale STANDARD_DEVIATION 8.7 • n=5 Participants
Functional Assessment of Chronic Illness-Fatigue (FACIT-F; total score)	70.0 units on a scale STANDARD_DEVIATION 10.9 • n=5 Participants	65.0 units on a scale STANDARD_DEVIATION 10.4 • n=7 Participants	70.0 units on a scale STANDARD_DEVIATION 10.6 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

The change of body weight(kg)will be measured between day 1 and day (Day 7-Day 1).

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Change of Body Weight	0 kg Standard Error 0.3	0.2 kg Standard Error 0.2

PRIMARY outcome

Timeframe: 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

The change of IGF-1 plasma levels will be measured between day 1 (prior to dosing) and day 7.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Change of Insulin-like Growth Factor-1 (IGF-1) Plasma Levels	9 ng/mL Standard Error 6.7	23 ng/mL Standard Error 3.9

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Change of Quality of Life Score ASAS	13.5 score on a scale Standard Deviation 5.1	6.7 score on a scale Standard Deviation 7.8
Change of Quality of Life Score FACIT-F	0.9 score on a scale Standard Deviation 4.7	0.2 score on a scale Standard Deviation 5.3

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Food Intake and Diary Test Meal Caloric Intake	59 kCals Standard Error 123	-78 kCals Standard Error 130
Food Intake and Diary Food Diary	-211 kCals Standard Error 243.1	96.1 kCals Standard Error 343

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Appetite (Visual Analog Scale [VAS] for Appetite)	7 units on a scale Standard Error 11.3	-27.5 units on a scale Standard Error 23.6

SECONDARY outcome

Timeframe: 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

Change in muscle strength as measured by handgrip strength.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Handgrip Strength	1.3 kg Standard Error 0.9	1.4 kg Standard Error 0.5

SECONDARY outcome

Timeframe: 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

Change in energy expenditure as measured by indirect calorimetry.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Energy Expenditure as Measured by Indirect Calorimetry.	49 kcals Standard Error 51	34 kcals Standard Error 49

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Laboratory Assays IGFBP-3	0.25 mcg/mL Standard Error 0.1	0.1 mcg/mL Standard Error 0.2
Laboratory Assays hs-CRP	-0.5 mcg/mL Standard Error 0.4	-0.4 mcg/mL Standard Error 0.4
Laboratory Assays Glucose	10 mcg/mL Standard Error 230	-35 mcg/mL Standard Error 95

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC)

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (White Blood Cells)	0.2 10^9 cells/L Standard Error 0.5	0.6 10^9 cells/L Standard Error 1.4

SECONDARY outcome

Timeframe: 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

Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
ECG Pre-Dose QT Corrected for HR Interval (QTC; ms)	3 ms Standard Error 13.8	-4 ms Standard Error 8.3
ECG Post-Dose PR Interval (ms)	-4 ms Standard Error 5.1	-4 ms Standard Error 65.7
ECG Post-Dose QRS Complex (ms)	2 ms Standard Error 1	3 ms Standard Error 4.5
ECG Post-Dose QT Interval (ms)	0 ms Standard Error 8.8	-17 ms Standard Error 17.82
ECG Post-Dose QTC (ms)	4 ms Standard Error 3.5	-8.5 ms Standard Error 17.3
ECG Pre-Dose QRS Complex (ms)	0 ms Standard Error 1.2	3 ms Standard Error 2.4
ECG Pre-Dose QT Interval (ms)	5 ms Standard Error 31.4	-11 ms Standard Error 13.4
ECG Pre-Dose PR Interval (ms)	0 ms Standard Error 4.3	2 ms Standard Error 5.9

SECONDARY outcome

Timeframe: 7 days

Recording of any adverse events from day 1 to day 7.

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=5 Participants Placebo: placebo (Powerade®) daily for 7 days.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Non-Serious, Unrelated Adverse Event	2 Participants	0 Participants
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Unrelated, Serious Adverse Event	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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

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))

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Change in Stair Climbing Power (SCP)	-5.1 W Standard Error 8.8	-5.9 W Standard Error 5.3

SECONDARY outcome

Timeframe: 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

Change in percent predicted (REE) as measured by indirect calorimetry.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Change in Percent Predicted Resting Energy Expenditure (REE)	4 % of predicted REE used Standard Error 3.7	3 % of predicted REE used Standard Error 4.2

SECONDARY outcome

Timeframe: 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

Change in respiratory quotient (the ratio of volume CO2 released to volume of O2 utilized) as measured by indirect calorimetry.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Change in Respiratory Quotient	-0.01 Ratio Standard Error 0.02	-0.01 Ratio Standard Error 0.01

SECONDARY outcome

Timeframe: 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

Change in Growth Hormone (GH) between day 1 and day 7.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Laboratory Assays (Growth Hormone)	0.7 ng/mL Standard Error 1.2	-0.5 ng/mL Standard Error 1

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC)

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Red Blood Cells)	0.1 10^6 cells/mcL Standard Error 0.1	-0.4 10^6 cells/mcL Standard Error 0.1

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC) and complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) HGB	0.3 g/dL Standard Error 0.2	-0.7 g/dL Standard Error 0.4
Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) MCH Concentration	0.3 g/dL Standard Error 0.2	0.4 g/dL Standard Error 0.2
Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) Protein	0.3 g/dL Standard Error 0.7	-0.3 g/dL Standard Error 0.2
Safety Laboratory (Hemoglobin [HGB]; Mean Corpuscular Hemoglobin [MCH] Concentration; Protein; Total Albumin) Total Albumin	0.1 g/dL Standard Error 0.3	-0.1 g/dL Standard Error 0.6

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC)

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) HCT	0.7 % of cells Standard Error 0.8	-2.3 % of cells Standard Error 1
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) RCDW	0 % of cells Standard Error 0.3	0 % of cells Standard Error 0.2
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) Neutrophil	5.9 % of cells Standard Error 7.2	1.2 % of cells Standard Error 11.4
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) Monocyte	0.9 % of cells Standard Error 2	-0.8 % of cells Standard Error 0.8
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) Eosinophil	-0.1 % of cells Standard Error 1.3	-0.7 % of cells Standard Error 3.1
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) Basophil	0.1 % of cells Standard Error 0.1	0.7 % of cells Standard Error 0.3
Laboratory Safety (Hematocrit [HCT]; Red Cell Distribution Width [RCDW]; Neutrophil; Lymphocyte; Monocyte; Eosinophil; Basophil) Lymphocyte	-0.1 % of cells Standard Error 5.5	0.4 % of cells Standard Error 7.3

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC)

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Mean Corpuscular Volume [MCV])	-0.1 fl Standard Error 7	-0.2 fl Standard Error 0.4

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC)

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Mean Corpuscular Hemoglobin [MCH])	0.2 pg Standard Error 0.2	0.3 pg Standard Error 0.1

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete blood count (CBC)

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Platelet)	14.5 10^3 cells/mcL Standard Error 21.9	10.5 10^3 cells/mcL Standard Error 9.3

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) BUN	-1.5 mg/dL Standard Error 1.3	2 mg/dL Standard Error 0.9
Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) Creatinine	0 mg/dL Standard Error 0.1	-0.03 mg/dL Standard Error 0
Safety Laboratory {Blood Urea Nitrogen [BUN]; Creatinine; Calcium) Calcium	0.2 mg/dL Standard Error 0.3	0 mg/dL Standard Error 0.1

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Sodium; Chloride; Carbon Dioxide) Sodium	0 mEq/L Standard Error 0.9	1 mEq/L Standard Error 0.9
Safety Laboratory (Sodium; Chloride; Carbon Dioxide) Chloride	-1 mEq/L Standard Error 1.3	2 mEq/L Standard Error 1.5
Safety Laboratory (Sodium; Chloride; Carbon Dioxide) Carbon Dioxide	0 mEq/L Standard Error 0.7	-2 mEq/L Standard Error 1.5

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Potassium)	0 mmol/L Standard Error 0.1	-0.4 mmol/L Standard Error 0.6

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Alkaline Phosphatase)	3 IU/L Standard Error 5.4	-4 IU/L Standard Error 4.3

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Estimated Glomerular Filtration Rate [eGFR])	-3.9 mL/min/1.73 m^2 Standard Error 4.8	3.4 mL/min/1.73 m^2 Standard Error 4.3

SECONDARY outcome

Timeframe: 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

Change in Clinical laboratory parameters: complete metabolic panel

Outcome measures

Measure	Macimorelin n=10 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) ALT	-2 U/L Standard Error 2.5	0 U/L Standard Error 0.6
Safety Laboratory (Alanine Transaminase [ALT]; Aspartate Aminotransferase [AST]) AST	0.5 U/L Standard Error 5.9	1.5 U/L Standard Error 1.4

SECONDARY outcome

Timeframe: 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

Change in electrocardiogram (ECG) at days 1 and 7 before and 1 hour after dosing and on the post-study visit.

Outcome measures

Measure	Macimorelin n=9 Participants Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=4 Participants Placebo: placebo (Powerade®) daily for 7 days.
ECG (Heart Rate [HR]) Pre-Dose HR	2.5 bpm Standard Error 2.7	2.5 bpm Standard Error 2.9
ECG (Heart Rate [HR]) Post-Dose HR	-1 bpm Standard Error 4.6	3 bpm Standard Error 1.8

Adverse Events

Macimorelin

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Macimorelin n=10 participants at risk Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=5 participants at risk Placebo: placebo (Powerade®) daily for 7 days.
Infections and infestations Forearm Soft Tissue Necrosis	10.0% 1/10 • Number of events 1 • From consenting to 16 days post last study visit (~23 days)	0.00% 0/5 • From consenting to 16 days post last study visit (~23 days)

Other adverse events

Measure	Macimorelin n=10 participants at risk Macimorelin: Subjects will receive macimorelin (1 mg/kg) and matching placebo (Powerade®) daily for 7 days.	Placebo n=5 participants at risk Placebo: placebo (Powerade®) daily for 7 days.
Gastrointestinal disorders Recurrent Abdominal Pain	10.0% 1/10 • Number of events 1 • From consenting to 16 days post last study visit (~23 days)	0.00% 0/5 • From consenting to 16 days post last study visit (~23 days)
Gastrointestinal disorders Recurrent Nausea	10.0% 1/10 • Number of events 1 • From consenting to 16 days post last study visit (~23 days)	0.00% 0/5 • From consenting to 16 days post last study visit (~23 days)
Infections and infestations Recurrent Herpes Breakout	10.0% 1/10 • Number of events 1 • From consenting to 16 days post last study visit (~23 days)	0.00% 0/5 • From consenting to 16 days post last study visit (~23 days)
Musculoskeletal and connective tissue disorders Pedal Oedema	10.0% 1/10 • Number of events 1 • From consenting to 16 days post last study visit (~23 days)	0.00% 0/5 • From consenting to 16 days post last study visit (~23 days)

Additional Information

Jose Garcia, MD, PhD

Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System

Phone: (206) 764-2984

Email: jg77@uw.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place