Trial Outcomes & Findings for Dolcanatide in Preventing Colorectal Cancer in Healthy Volunteers (NCT NCT03300570)

Last Updated: 2021-06-14

Results Overview

Pharmacological effect on cyclic guanosine monophosphate (cGMP) levels for dolcanatide arm versus (vs.) placebo, where this effect is defined as the arithmetic difference in mean cGMP levels before and after 7 days of dolcanatide from subject biopsies. This represents the increase in cGMP stimulated by 7 days of dolcanatide in an individual subject. The mean cGMP value will be calculated based on 6 biopsies collected from the rectum during a flexible sigmoidoscopy procedure. Each biopsy was analyzed in triplicate using a commercially available EIA kit.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

27 participants

Primary outcome timeframe

Baseline to 7 days

Results posted on

2021-06-14

Participant Flow

37 patients were pre-registered, where 10 were screen failures, leaving 27 patients who proceeded to randomization.

Participant milestones

Participant milestones
Measure	Arm A (Placebo) Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with placebo.	Arm B (Dolcanatide) Participants receive dolcanatide PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.
Overall Study STARTED	13	14
Overall Study COMPLETED	11	13
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Placebo) Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with placebo.	Arm B (Dolcanatide) Participants receive dolcanatide PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.
Overall Study Adverse Event	0	1
Overall Study Withdrawal by Subject	1	0
Overall Study Inadequate bowel prep	1	0

Baseline Characteristics

Dolcanatide in Preventing Colorectal Cancer in Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Placebo) n=13 Participants Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with placebo.	Arm B (Dolcanatide) n=14 Participants Participants receive dolcanatide PO QD for 7 days.All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.	Total n=27 Participants Total of all reporting groups
Age, Continuous	44.2 years STANDARD_DEVIATION 11.67 • n=5 Participants	48.7 years STANDARD_DEVIATION 5.72 • n=7 Participants	46.6 years STANDARD_DEVIATION 9.19 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	14 Participants n=7 Participants	23 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	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	6 Participants n=7 Participants	9 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status = 0	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 7 days

Population: Only patients who completed the study in the Participant Flow are included in this analysis.

Outcome measures

Outcome measures
Measure	Arm B (Dolcanatide) n=13 Participants Participants receive dolcanatide PO QD for 7 days.All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.	Arm A (Placebo) n=11 Participants Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with placebo.
Pharmacological Effect on Cyclic Guanosine Monophosphate (cGMP) Levels for Dolcanatide Arm Versus (vs.) Placebo, as Measured by the Differences in Mean cGMP Levels After 7 Days of Intervention	-0.42 pmol/mg Standard Deviation 0.43	-0.22 pmol/mg Standard Deviation 0.29

SECONDARY outcome

Timeframe: Baseline to 7 days

Each participant will be assessed for PD response. The calculation is based on the standardized difference in means for the pharmacological effect on cGMP levels at the participant level, where a subject with a z \>= 1.645 will be considered a PD responder. A participant with a z \< 1.645 will be considered a non-responder. The PD response rate (percentage) of patients are summarized below by arm.

Outcome measures

Outcome measures
Measure	Arm B (Dolcanatide) n=13 Participants Participants receive dolcanatide PO QD for 7 days.All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.	Arm A (Placebo) n=11 Participants Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with placebo.
Pharmacodynamic (PD) Response Rate	0 percentage of patients	0 percentage of patients

SECONDARY outcome

Timeframe: Up to 21 days

The overall adverse event rates (percentages) for grade 3 or higher adverse events regardless of attribution to treatment are reported below. The percentages below are summarized for Diarrhea.

Outcome measures

Outcome measures
Measure	Arm B (Dolcanatide) n=14 Participants Participants receive dolcanatide PO QD for 7 days.All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.	Arm A (Placebo) n=13 Participants Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with placebo.
Percentage of Participants With Grade 3 or Higher Diarrhea Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	7.1 percentage of patients	0 percentage of patients

Adverse Events

Arm A (Placebo)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Arm B (Dolcanatide)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

David Weinberg, M.D., M.Sc.

Fox Chase Cancer Center

Phone: 215-214-1424

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A (Placebo) n=13 participants at risk Participants receive placebo PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing withplacebo.	Arm B (Dolcanatide) n=14 participants at risk Participants receive dolcanatide PO QD for 7 days. All participants will undergo sigmoidoscopies at baseline and after seven days of daily dosing with dolcanatide.
Gastrointestinal disorders Bloating	7.7% 1/13 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	0.00% 0/14 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Constipation	7.7% 1/13 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Diarrhea	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	78.6% 11/14 • Number of events 48 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Dry mouth	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Dyspepsia	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 5 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Flatulence	7.7% 1/13 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Gastrointestinal disorders Vomiting	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	14.3% 2/14 • Number of events 2 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
General disorders Fatigue	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Metabolism and nutrition disorders Anorexia	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	0.00% 0/14 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Nervous system disorders Dizziness	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Psychiatric disorders Anxiety	7.7% 1/13 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	0.00% 0/14 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Respiratory, thoracic and mediastinal disorders Voice alteration	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 1 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.
Skin and subcutaneous tissue disorders Skin and subcut tissue disord - Oth spec	0.00% 0/13 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.	7.1% 1/14 • Number of events 4 • Up to 21 days Each CTCAE term is a representation of a specific event used for medical documentation \& analysis \& is a single MedDRA Lowest Level Term (LLT). Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, \& appear in the SAE table.