Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia

The drug being tested in this study is called TAK-831. TAK-831 is being tested to treat
people who have Friedreich ataxia. This study will look at upper extremity (arms and hands)
motor function and manual dexterity of people who take TAK-831. Efficacy evaluations also
include other neurological, functional, and patient performance assessments.

The study will enroll approximately 65 participants. Participants will be randomly assigned
in a 2:1:2 ratio to one of the three treatment groups—which will remain undisclosed to the
participant and study doctor during the study (unless there is an urgent medical need):

- TAK-831 High dose

- TAK-831 Low dose

- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has
no active ingredient

All participants will be asked to take three tablets of high dose, low dose, or placebo twice
a day for 12 weeks.

This multi-center trial will be conducted in the United States. The overall time to
participate in this study is approximately 13 weeks. Participants will make 5 visits to the
clinic, and will be contacted by telephone for an exit interview no later than 7 days after
their final visit or termination. Participants will also receive a safety follow-up phone
call 7 to 17 days after receiving their last dose of TAK-831.

Key Inclusion Criteria:

1. Has a genetically-confirmed diagnosis (homozygous for guanine-adenine-adenine [GAA]
repeat expansions in the frataxin gene [FXN] in the affected range of Friedreich ataxia
[FRDA] or a compound heterozygous expansion with a point mutation or deletion), with an
established disease stage of 2 to 5, inclusive, as determined by the Functional Staging for
Ataxia, at Screening.

Key Exclusion Criteria:

1. Received a diagnosis of ataxic syndromes other than FRDA.

2. Has a history of cancer, except basal cell carcinoma or in situ cervical cancer that
has been in remission for greater than or equal to (>=5) years prior to first dose of
study drug.

3. Known to be currently infected or has been infected with human immunodeficiency virus
(HIV), hepatitis B virus, or hepatitis C virus.

4. Has a known hypersensitivity to any component of the formulation of TAK-831.

5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse.

6. Has taken any excluded medication, or has had insufficient washout of medications or
is unable or unwilling to discontinue medications as required by the protocol.

7. If male, the participant intends to donate sperm during the course of this study or
for 95 days after the last dose of study drug.

8. If female, the participant is of childbearing potential and lactating, pregnant
(positive prerandomization serum pregnancy test), or plans to become pregnant before
participating in the study, during the study, or within 35 days after last dose of the
study drug, or intending to donate ova during such time period.

9. Has a history of neuroleptic malignant syndrome, water intoxication, or paralytic
ileus or other conditions that may interfere with absorption of study medication.