Trial Outcomes & Findings for Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma (NCT NCT02949700)

Last Updated: 2023-06-29

Results Overview

Dose limiting toxicities include diarrhea/gastrointestinal disturbance and hypoglycemia requiring dose reduction, and they will be measured for the time frame detailed above. Adverse Events (AE)s will be graded in accordance with the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE) http://ctep.cancer.gov/ reporting/ctc.html. If not described in the NCI-CTCAE, AEs will be graded according to their severity using the following criteria: grade 1 (mild), grade 2 (moderate), grade 3 (severe), and grade 4 (life threatening).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

26 participants

Primary outcome timeframe

treatment duration plus 30 days following treatment (an average of 13 weeks)

Results posted on

2023-06-29

Participant Flow

One subject withdrew consent prior to being assigned to a dose level. Therefore, 25 patients were assigned dose levels and began treatment.

Participant milestones

Participant milestones
Measure	Single Arm, Treatment: DL1 (Phase I) Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1 (DL1): 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2 (DL2): 1500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL-1 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level -1 (DL-1): 500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL1 (Phase II) Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1 (DL1): 850 mg per os (PO) twice daily (BID)
Phase I STARTED	9	3	0	0
Phase I COMPLETED	7	2	0	0
Phase I NOT COMPLETED	2	1	0	0
Phase II STARTED	0	0	1	12
Phase II COMPLETED	0	0	0	7
Phase II NOT COMPLETED	0	0	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Single Arm, Treatment: DL1 (Phase I) Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1 (DL1): 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2 (DL2): 1500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL-1 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level -1 (DL-1): 500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL1 (Phase II) Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1 (DL1): 850 mg per os (PO) twice daily (BID)
Phase I Withdrawal by Subject	1	1	0	0
Phase I Protocol Violation	1	0	0	0
Phase II Withdrawal by Subject	0	0	0	2
Phase II Protocol Violation	0	0	1	3

Baseline Characteristics

Phase I/II Study OF Metformin in Combination With Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Arm, Treatment: DL1 (Phase I) n=9 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 n=3 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2: 1500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL-1 n=1 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL1 (Phase II) n=12 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Total n=25 Participants Total of all reporting groups
Age, Continuous	60.8 years STANDARD_DEVIATION 7.5 • n=5 Participants	69.0 years STANDARD_DEVIATION 7.5 • n=7 Participants	64.0 years STANDARD_DEVIATION 0.0 • n=5 Participants	58.6 years STANDARD_DEVIATION 6.3 • n=4 Participants	60.8 years STANDARD_DEVIATION 7.3 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants	24 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants	23 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	12 Participants n=4 Participants	23 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: treatment duration plus 30 days following treatment (an average of 13 weeks)

Population: Participants were considered for Phase I toxicity (dose-limiting toxicity) evaluation if they were enrolled in the Phase I portion and took 70% or more of the study drug throughout the course of the trial. 9 out of 25 subjects (7 on DL1 (Phase I), 2 on DL2) met this criterion.

Outcome measures

Outcome measures
Measure	Single Arm, Treatment: DL1 (Phase I) n=7 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 n=2 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2: 1500 mg per os (PO) twice daily (BID)
Phase I - Dose-Limiting Toxicity	0 dose-limiting toxicities	0 dose-limiting toxicities

PRIMARY outcome

Timeframe: Treatment duration plus 8-12 weeks following treatment completion (up to 21 weeks total)

Population: Participants were considered for Phase II efficacy (disease response rate) evaluation if they were enrolled in the Phase II portion and took 70% or more of the study drug throughout the course of the trial. 7 out of 25 subjects (7 on DL1 (Phase II)) met this criterion.

Response and progression will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST1.1) Committee \[Eur J Cancer. 2009 Jan; 45(2):228-47\]. Changes in only the largest diameter (uni-dimensional measurement) of the tumor lesions are used in the RECIST 1.1 criteria. For the purposes of this study, patients should be reevaluated for response following completion of treatment as per current institutional protocol for this disease site: 1) spiral contrast enhanced computed tomography (CECT) at 10 weeks following completion of treatment or 2) positron emission tomography (PET) at 12 weeks following completion of treatment. Per RECIST v1.1 criteria for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Disease response rate is defined as the percentage of patients with OR.

Outcome measures

Outcome measures
Measure	Single Arm, Treatment: DL1 (Phase I) n=7 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2: 1500 mg per os (PO) twice daily (BID)
Phase II - Efficacy (Disease Response Rate)	100.0 percentage of participants with response Interval 59.0 to 100.0	—

SECONDARY outcome

Timeframe: Date of study registration to recurrence/progression/death or up to 2 years following treatment completion, whichever comes first.

Population: Participants were considered for Phase II progression free survival evaluation if they were enrolled in the Phase II portion and took 70% or more of the study drug throughout the course of the trial. 7 out of 25 subjects (7 on DL1 (Phase II)) met this criterion.

Measurement of time from date of study registration to date of documented radiographic recurrence/progression or death.

Outcome measures

Outcome measures
Measure	Single Arm, Treatment: DL1 (Phase I) n=7 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2: 1500 mg per os (PO) twice daily (BID)
Phase II - Progression Free Survival	22.7 months Interval 9.8 to 29.3	—

SECONDARY outcome

Timeframe: Date of study registration to death or up to 2 years following treatment completion, whichever comes first.

Population: Participants were considered for Phase II overall survival evaluation if they were enrolled in the Phase II portion and took 70% or more of the study drug throughout the course of the trial. 7 out of 25 subjects (7 on DL1 (Phase II)) met this criterion.

Measurement of time from date of study registration to date of death.

Outcome measures

Outcome measures
Measure	Single Arm, Treatment: DL1 (Phase I) n=7 Participants Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2: 1500 mg per os (PO) twice daily (BID)
Phase II - Overall Survival	22.7 months Interval 9.8 to 29.3	—

Adverse Events

Single Arm, Treatment: DL1 (Phase I)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 4 deaths

Single Arm, Treatment: DL2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Single Arm, Treatment: DL-1

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Single Arm, Treatment: DL1 (Phase II)

Serious events: 3 serious events

Other events: 12 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Single Arm, Treatment: DL1 (Phase I) n=9 participants at risk Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL2 n=3 participants at risk Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 2: 1500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL-1 n=1 participants at risk Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level -1: 500 mg per os (PO) twice daily (BID)	Single Arm, Treatment: DL1 (Phase II) n=12 participants at risk Patients in the Phase I trial will be assigned to a single arm, experimental treatment which will test dose escalation for metformin in the context of chemo-radiation, with toxicity as the primary outcome. Patients in the Phase II trial will be assigned to a single arm (DL1), experimental treatment consisting of metformin plus chemo-radiation. Metformin: Metformin will be administered orally twice daily during treatment with chemo-radiation for head and neck squamous cell carcinoma. This will occur 7 to 11 days prior to chemotherapy and radiation. Dose Level 1: 850 mg per os (PO) twice daily (BID)
Cardiac disorders Heart failure	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Cardiac disorders Ventricular tachycardia	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Infections and infestations Lung infection	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Investigations Creatinine increased	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	33.3% 1/3 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Metabolism and nutrition disorders Dehydration	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Nervous system disorders Syncope	11.1% 1/9 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 2 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Renal and urinary disorders Acute kidney injury	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	33.3% 1/3 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/12 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	33.3% 1/3 • Number of events 1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/12 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.
Vascular disorders Hypotension	0.00% 0/9 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/3 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	0.00% 0/1 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.	8.3% 1/12 • Number of events 2 • The AE collection/reporting period began with the first day of treatment with metformin and was completed at 30 days following treatment completion of each participant. This resulted in a 13 week period of AE collecting/reporting for each participant. All-cause mortality data was collected up to 2 years following treatment completion, as per Outcome Measure 4.

Other adverse events

Additional Information

Dr. Vlad Sandulache

Baylor College of Medicine

Phone: 713-798-7218

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place