Trial Outcomes & Findings for Romidepsin Plus Oral 5-Azacitidine in Relapsed/Refractory Lymphoid Malignancies (NCT NCT01998035)

NCT ID: NCT01998035

Last Updated: 2024-08-22

Results Overview

The highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 58 participants
• Primary outcome timeframe: up to 1.5 years
• Results posted on: 2024-08-22

Participant Flow

From November 2013 through January 2016, 33 patients were enrolled, and 7 withdrew from the study before receiving the study interventions. 26 patients received the study interventions in Phase 1. From April 2017 and March 2019, 25 patients were enrolled in Phase 2 and received the study interventions.

The participants in Phase 1 (n=26) are a different population than the participants in Phase 2 (n=25).

Participant milestones

Measure	Phase 1, Dose Level 1: Oral 5-Azacitidine 100 mg and Romidepsin 10 mg/m2 Cohort 1: Participants were administered 100 mg of oral 5-Azacitidine (Days 1-14) and 10 mg/m2 of Romidepsin (Days 8 and 15) every 21 days	Phase 1, Dose Level 2: Oral 5-Azacitidine 200 mg and Romidepsin 10 mg/m2 Cohort 2: Participants were administered 200 mg of oral 5-Azacitidine (Days 1-14) and 10 mg/m2 of Romidepsin (Days 8 and 15) every 21 days	Phase 1, Dose Level 3: Oral 5-Azacitidine 200 mg and Romidepsin 10 mg/m2 (Extended Cycle) Cohort 3: Participants were administered 200 mg of oral 5-Azacitidine (Days 1-14) and 10 mg/m2 of Romidepsin (Days 8 and 15) every 28 days	Phase 1, Dose Level 4: Oral 5-Azacitidine 300 mg and Romidepsin 10 mg/m2 Cohort 4: Participants were administered 300 mg of oral 5-Azacitidine (Days 1-14) and 10 mg/m2 of Romidepsin (Days 8 and 15) every 28 days	Phase 1, Dose Level 5: Oral 5-Azacitidine 300 mg and Romidepsin 14 mg/m2 Cohort 5: Participants were administered 300 mg of oral 5-Azacitidine (Days 1-14) and 14 mg/m2 of Romidepsin (Days 8, 15, and 22) every 28 days	Phase 1, Dose Level 6: Oral 5-Azacitidine 300 mg and Romidepsin 14 mg/m2 Cohort 6: Participants were administered 300 mg of oral 5-Azacitidine (Days 1-14) and 14mg/m2 of Romidepsin (Days 8, 15, and 22) every 35 days. Determined to be the Maximum Tolerated Dose (MTD) i.e. the Recommended Phase 2 Dose (RP2D)	Phase 1, Dose Level 6 (MTD): Oral 5-Azacitidine 300 mg and Romidepsin 14 mg/m2 Expanded Cohort 6: Participants were administered 300 mg of oral 5-Azacitidine (Days 1-21) and 14 mg/m2 of Romidepsin (Days 8, 15, and 22) every 35 days. Determined to be the MTD (Maximum Administrable Dose)	Phase 2, MTD: Oral 5-Azacitidine 300 mg and Romidepsin 14 mg/m2 Patients will be treated with oral 5-azacytidine and Romidepsin at the MTD. The treatment will be administered as follows: oral 5-azacytidine 300 mg (flat dose) on Days 1-14 and Romidepsin 14 mg/m2 (flat dose) on Days 8, 15, and 22 on a 35-day cycle.
Phase 1: Dose Level 1 STARTED	6	0	0	0	0	0	0	0
Phase 1: Dose Level 1 COMPLETED	6	0	0	0	0	0	0	0
Phase 1: Dose Level 1 NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 1: Dose Level 2 STARTED	0	3	0	0	0	0	0	0
Phase 1: Dose Level 2 COMPLETED	0	3	0	0	0	0	0	0
Phase 1: Dose Level 2 NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 1: Dose Level 3 STARTED	0	0	3	0	0	0	0	0
Phase 1: Dose Level 3 COMPLETED	0	0	3	0	0	0	0	0
Phase 1: Dose Level 3 NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 1: Dose Level 4 STARTED	0	0	0	3	0	0	0	0
Phase 1: Dose Level 4 COMPLETED	0	0	0	3	0	0	0	0
Phase 1: Dose Level 4 NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 1: Dose Level 5 STARTED	0	0	0	0	3	0	0	0
Phase 1: Dose Level 5 COMPLETED	0	0	0	0	3	0	0	0
Phase 1: Dose Level 5 NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 1: Dose Level 6 STARTED	0	0	0	0	0	3	0	0
Phase 1: Dose Level 6 COMPLETED	0	0	0	0	0	3	0	0
Phase 1: Dose Level 6 NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 1: Dose Level 6 (Expanded Cohort) STARTED	0	0	0	0	0	0	5	0
Phase 1: Dose Level 6 (Expanded Cohort) COMPLETED	0	0	0	0	0	0	5	0
Phase 1: Dose Level 6 (Expanded Cohort) NOT COMPLETED	0	0	0	0	0	0	0	0
Phase 2: MTD STARTED	0	0	0	0	0	0	0	25
Phase 2: MTD COMPLETED	0	0	0	0	0	0	0	25
Phase 2: MTD NOT COMPLETED	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Romidepsin Plus Oral 5-Azacitidine in Relapsed/Refractory Lymphoid Malignancies

Baseline characteristics by cohort

Measure	Phase 1 n=33 Participants Phase 1 is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. Patients will be administered the study drugs in a 3 + 3 dose-escalation study.	Phase 2 n=25 Participants Patients will be treated with oral 5-azacytidine and Romidepsin at the MTD. The treatment will be administered as follows: oral 5-azacytidine 300 mg (flat dose) on Days 1-14 and Romidepsin 14 mg/m2 (flat dose) on Days 8, 15, and 22 on a 35-day cycle.	Total n=58 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	63 years n=7 Participants	NA years n=5 Participants
Sex/Gender, Customized Female	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Sex/Gender, Customized Male	19 Participants n=5 Participants	15 Participants n=7 Participants	34 Participants n=5 Participants
Sex/Gender, Customized Unknown	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 1.5 years

Population: This Outcome Measure is specific for Phase 1 of the study. This Outcome Measure was NOT applied to Phase 2, therefore data was only collected and reported for Phase 1. 26 participants received the study interventions in Phase 1.

The highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

Outcome measures

Measure	Phase I n=26 Participants Phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. The safety and toxicity of this combination will be evaluated throughout the entire study.
Phase I: Maximum Tolerated Dose (MTD) of the Combination of Oral 5-azacitidine in Combination With Romidepsin	300 mg

PRIMARY outcome

Timeframe: up to 1.5 years

Population: This Outcome Measure is specific for Phase 1 of the study. This Outcome Measure was NOT applied to Phase 2, therefore data was only collected and reported for Phase 1. 26 participants received the study interventions in Phase 1.

The highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found.

Outcome measures

Measure	Phase I n=26 Participants Phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. The safety and toxicity of this combination will be evaluated throughout the entire study.
Phase I: Maximum Tolerated Dose (MTD) of Romidepsin in Combination With Oral 5-azacytidine	14 mg/m2

PRIMARY outcome

Timeframe: Up to 1.5 years

Population: This Outcome Measure is specific for Phase 1 of the study. This Outcome Measure was NOT applied to Phase 2, therefore data was only collected and reported for Phase 1. Results were not collected per dose level and thus cannot be reported per dose level. 26 participants received the study interventions in Phase 1.

Patients receiving the combination of oral 5-azacitidine and romidepsin and experiencing grades 1-4 toxicities will be tallied based on events observed and assessed by a qualified investigator. This Outcome Measure is specifically for Phase 1 of the study.

Outcome measures

Measure	Phase I n=26 Participants Phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. The safety and toxicity of this combination will be evaluated throughout the entire study.
Percentage of Patients Who Experienced Significant Toxicities in Phase 1	10 percentage of participants

PRIMARY outcome

Timeframe: Up to 3 years

Population: This Outcome Measure is specific for Phase 2 of the study, therefore data was only collected and reported for Phase 2. Results were not collected per dose level and thus cannot be reported per dose level.

The percentage of people in a study or treatment group who have a partial response or complete response to the treatment within a certain period of time. A partial response is a decrease in the size of a tumor or in the amount of cancer in the body, and a complete response is the disappearance of all signs of cancer in the body. In a clinical trial, measuring the ORR is one way to see how well a new treatment works.

Outcome measures

Measure	Phase I n=25 Participants Phase I is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. The safety and toxicity of this combination will be evaluated throughout the entire study.
Phase II: Overall Response Rate (ORR) (Complete + Partial Response) of the Combination of Oral 5-azacitidine and Romidepsin in Patients With Relapsed/Refractory T-Cell Lymphoma	30 percentage of participants

Adverse Events

Phase 1

Serious events: 11 serious events

Other events: 26 other events

Deaths: 11 deaths

Phase 2

Serious events: 12 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Measure	Phase 1 n=26 participants at risk Phase 1 is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. Patients will be administered the study drugs in a 3 + 3 dose-escalation study. Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor". Dose escalation: 10, 14 mg/m2 Oral 5-Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Dose escalation: 100, 200, 300 mg	Phase 2 n=25 participants at risk Patients will be treated with oral 5-azacytidine and romidepsin at the MTD. The treatment will be administered as follows: oral 5-azacytidine 300 mg (flat dose) on Days 1-14 and romidepsin 14 mg/m2 (flat dose) on Days 8, 15, and 22 on a 35-day cycle.
General disorders Alkaline phosphatase elevation	3.8% 1/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	0.00% 0/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Blood and lymphatic system disorders Anemia	19.2% 5/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	16.0% 4/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Febrile neutropenia	7.7% 2/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	12.0% 3/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Endocrine disorders Hyperglycemia (Grade 3 and 4)	3.8% 1/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	4.0% 1/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Renal and urinary disorders Hypermagnesemia	3.8% 1/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	0.00% 0/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Hypokalemia	3.8% 1/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	0.00% 0/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Hyponatremia	7.7% 2/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	0.00% 0/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Hypotension	11.5% 3/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	0.00% 0/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Immune system disorders Lymphocyte count decrease	42.3% 11/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	32.0% 8/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Immune system disorders Neutrophil count decrease	42.3% 11/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	40.0% 10/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Immune system disorders Platelet count decrease	26.9% 7/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	48.0% 12/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.

Other adverse events

Measure	Phase 1 n=26 participants at risk Phase 1 is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of oral 5-azacitidine and romidepsin in patients with lymphoma. Patients will be administered the study drugs in a 3 + 3 dose-escalation study. Romidepsin is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Romidepsin is classified as a "Histone Deacetylase Inhibitor". Dose escalation: 10, 14 mg/m2 Oral 5-Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Dose escalation: 100, 200, 300 mg	Phase 2 n=25 participants at risk Patients will be treated with oral 5-azacytidine and romidepsin at the MTD. The treatment will be administered as follows: oral 5-azacytidine 300 mg (flat dose) on Days 1-14 and romidepsin 14 mg/m2 (flat dose) on Days 8, 15, and 22 on a 35-day cycle.
General disorders Fatigue	38.5% 10/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	52.0% 13/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Nausea	53.8% 14/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	60.0% 15/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Vomiting	46.2% 12/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	40.0% 10/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Renal and urinary disorders Creatinine elevation	30.8% 8/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	40.0% 10/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Gastrointestinal disorders Diarrhea	26.9% 7/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	48.0% 12/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Fever	11.5% 3/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	28.0% 7/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Blood and lymphatic system disorders Hypercalcemia	11.5% 3/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	12.0% 3/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Hypoalbuminemia	50.0% 13/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	44.0% 11/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Blood and lymphatic system disorders Hypocalcemia	19.2% 5/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	28.0% 7/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
General disorders Hypoglycemia	11.5% 3/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	12.0% 3/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.
Endocrine disorders Hyperglycemia (Grade 1 and 2)	80.8% 21/26 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.	56.0% 14/25 • 1.5 years Adverse events were only recorded/collected as the combined total from participants per study phase. Adverse events were not collected per dose level and thus cannot be reported per dose level. For Phase 1, adverse events were collected from the 26 participants who received the study interventions and completed the study.

Additional Information

Ana Ignat

Columbia University Irving Medical Center

Phone: 212-305-3612

Email: ai2111@cumc.columbia.edu

Results disclosure agreements

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