Trial Outcomes & Findings for Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy (NCT NCT01313117)

NCT ID: NCT01313117

Last Updated: 2014-10-02

Results Overview

Based on acceptable adverse event (AE) profile and continual reassessment method dose escalation.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 9 participants
• Primary outcome timeframe: 4 months
• Results posted on: 2014-10-02

Participant Flow

Participant milestones

Measure	Alpha Lipoic Acid Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Cohort 1: Dose Level 1 (ALA 300mg Daily) STARTED	2
Cohort 1: Dose Level 1 (ALA 300mg Daily) COMPLETED	2
Cohort 1: Dose Level 1 (ALA 300mg Daily) NOT COMPLETED	0
Cohort 2: Dose Level 2 (ALA 600mg Daily) STARTED	2
Cohort 2: Dose Level 2 (ALA 600mg Daily) COMPLETED	1
Cohort 2: Dose Level 2 (ALA 600mg Daily) NOT COMPLETED	1
Cohort 3: Dose Level 3 (ALA 400mg Daily) STARTED	2
Cohort 3: Dose Level 3 (ALA 400mg Daily) COMPLETED	2
Cohort 3: Dose Level 3 (ALA 400mg Daily) NOT COMPLETED	0
Cohort 4: Dose Level 4 (ALA 500mg Daily) STARTED	2
Cohort 4: Dose Level 4 (ALA 500mg Daily) COMPLETED	2
Cohort 4: Dose Level 4 (ALA 500mg Daily) NOT COMPLETED	0
Cohort 5: Dose Level 2 (ALA 600mg Daily) STARTED	1
Cohort 5: Dose Level 2 (ALA 600mg Daily) COMPLETED	0
Cohort 5: Dose Level 2 (ALA 600mg Daily) NOT COMPLETED	1

Reasons for withdrawal

Measure	Alpha Lipoic Acid Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Cohort 2: Dose Level 2 (ALA 600mg Daily) Adverse Event	1
Cohort 5: Dose Level 2 (ALA 600mg Daily) Adverse Event	1

Baseline Characteristics

Alpha-lipoic Acid in Patients at Risk for Paclitaxel Induced Neuropathy

Baseline characteristics by cohort

Measure	Alpha Lipoic Acid n=9 Participants Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Age, Continuous	56.7 years n=93 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants
Sex: Female, Male Female	9 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Region of Enrollment United States	9 participants n=93 Participants

PRIMARY outcome

Timeframe: 4 months

Population: Although our dose finding analysis suggested a maximum tolerated dose of 500mg daily, it should be noted that we failed to fully complete the Continual Reassessment Method (CRM) dose finding portion of the study. As such, we can not make confident dose finding statements on the basis of this trial.

Based on acceptable adverse event (AE) profile and continual reassessment method dose escalation.

Outcome measures

Measure	Alpha Lipoic Acid n=9 Participants Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Identification of the Optimal Dose of ALA Based on Acceptable Adverse Event(AE) Profile	500 mg

SECONDARY outcome

Timeframe: 4 months

Outcome measures

Measure	Alpha Lipoic Acid n=9 Participants Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Proportion of Patients Who Complete the Proposed Regimen of Daily ALA	7 participants

SECONDARY outcome

Timeframe: 4 months

Outcome measures

Measure	Alpha Lipoic Acid n=9 Participants Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Cumulative Rate of Adverse Events	9 participants

SECONDARY outcome

Timeframe: 4 months

Population: Failure to reach the MTD precluded our ability to perform any meaningful analysis of the TNS.

The Total Neuropathy score (TNS) is a validated score that combines signs, symptoms, and very limited nerve conduction studies (NCS). It was designed to assess peripheral nerve function and has been used as an endpoint in clinical trials of toxic neuropathy. The TNS is a composite scale with a range of values from 0 (normal) to 28 (severely affected). It includes data from 7 different categories. Patients are asked to assess the severity of sensory symptoms on a scale of 0 (no symptoms) to 4 (symptoms above knees or elbows, or functionally disabling). Next, 4 examination categories are assessed. These include pin sensation, vibration sensation, deep tendon reflexes, and strength. Signs are scored from 0 to 4 depending on severity. The nerve conduction portion of the scale consists of measurements of a motor (peroneal) and sensory (sural) nerve. Motor and sensory responses are graded on a scale of 0 to 4 depending on the severity of an abnormality.

Outcome measures

Outcome data not reported

Adverse Events

Alpha Lipoic Acid

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Alpha Lipoic Acid n=9 participants at risk Oral administration three times daily (morning, mid-day, night) Alpha lipoic acid: The baseline dose is 100 mg three times daily for four months. Dose escalation will occur until a maximum tolerated dose is found.
Gastrointestinal disorders Nausea	33.3% 3/9 • Number of events 3
Skin and subcutaneous tissue disorders Rash	33.3% 3/9 • Number of events 3
Gastrointestinal disorders Indigestion	11.1% 1/9 • Number of events 1
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1
Gastrointestinal disorders Pain	11.1% 1/9 • Number of events 1

Additional Information

Jeffrey Allen M.D.

Northwestern University

Phone: 312-695-8636

Email: jallen1@nmff.org

Results disclosure agreements

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